Pressure control gaskets for operating pump cassette membranes

ABSTRACT

A pump cassette comprising an outer flexible membrane covering flowpaths, valve chambers and pump chambers of the cassette is designed to be actuated by a control gasket on a base unit arranged to move designated valve and pump portions of the cassette membrane. The gasket valve control or actuation region is at least partially bounded by a vacuum channel facing the outside of the gasket so that a constant vacuum can be applied between the gasket valve control or actuation region and the adjacent portion of the cassette membrane. An improved version of the vacuum channel comprises a flexible inner wall of the vacuum channel flexes or partially collapses away from the cassette valve seat, while still maintaining patency of the vacuum channel during the application of negative pressure on the gasket valve actuation region to open the cassette valve.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 15/462,497, entitled Pressure Control Gaskets for OperatingPump Cassette Membranes, filed on Mar. 17, 2017, and will be U.S. Pat.No. 10,578,092, issuing on Mar. 3, 2020, which claims priority to andthe benefit of U.S. Provisional Patent Application Ser. No. 62/310,361,filed on Mar. 18, 2016 and entitled Pressure Control Gaskets forOperating Pump Cassette Membranes, which is hereby incorporated hereinby reference in its entirety.

BACKGROUND

Fluid handling devices (an example of which is described herein as abase unit) can be configured to receive fluid pumping cassettes toactuate membrane-based pumps and valves on the cassette, with a goal ofdelivering fluid from various sources to various destinations. Anadvantage of such a system is that the cassette can be discarded after asingle use, obviating the need for sterilization and packaging forreuse, and the fluid handling device can remain free from contact withthe fluids being processed. Such a system can be used in any applicationin which fluid pumping is needed and in which disposable fluid-carryingcomponents (such as pump cassettes) are desirable. This is particularlyuseful in the medical field, because cleaning and sterilizationprocedures for repeated use of certain fluid-exposed equipment can beexpensive, unreliable, and may result in a reduced lifespan of theequipment. Disposable membrane-based pumping cassettes can be used inmany medical applications, including, for example, IV infusion devices,extracorporeal blood handling devices, hemodialysis/hemoperfusiondevices, body cavity irrigation devices, and automated peritonealdialysis devices. This technology can similarly be applied tonon-medical fluid handling systems in various industries, includingbiotechnology.

Pumping cassettes may comprise self-enclosed units that include both afluid flowpath side and an actuation side (commonly pneumatic actuationof membrane-based pumps and valves), the actuation side having one ormore attached diaphragms to operate the pumps and valves. The cassetteshave ports for connection to fluid sources and destinations. Theactuation side of the cassette is configured to be coupled or mated topressure actuation sources (potentially hydraulic, but more typicallypneumatic). Pumping cassettes may also comprise relatively flat, thinhousings that include fluid pathways, occludable valve orifices tocontrol the direction of fluid flow in the cassette, and the pumpingchamber portion of one or more membrane-based pumps. In one version,these cassettes are typically covered on one or both sides with aflexible membrane fused to the perimeter of the cassette, providing aliquid seal between the fluid paths within the cassette and the outsideenvironment. Both the on-board pumping chambers and valves are operatedby having a base unit provide actuation pressure (both positive andnegative pressure) to pump actuation regions and valve actuation regionsof the outer cassette membrane facing the base unit. This actuationpressure can be delivered by a valved manifold connected to positive andnegative pressure sources (e.g. tanks pressurized by separate pumps).The valved manifold can be configured to deliver positive or negativepressure to an installed pump cassette through the use ofcontroller-driven electromechanical valves installed in the manifold.The manifold can deliver the actuation pressure to various valves andpumps of the installed cassette through a pressure delivery block thatmates with the cassette, which when mated with adequate force, seals thecassette membrane against various walls defining flowpaths, valves andpumps in the cassette to form sealed fluid flowpaths within thecassette. The pressure delivery block includes pneumatic ports thatalign with the locations of various valves and pumps on the cassette.

In some embodiments, a gasket can be positioned against the face of thepressure delivery block, the gasket having elastomeric actuation regionsthat mate with corresponding regions on a cassette membrane when thecassette is installed on the base unit. In this arrangement, thepressure delivery block may also include vacuum ports that penetrate thegasket near the control regions so that a constant vacuum can be appliedbetween the gasket and the membrane of an installed cassette, so thatmovement of a gasket control region toward or away from the pressuredelivery block can be mimicked by the corresponding region of thecassette membrane. The gasket placed over the pressure delivery blockcan be made of rubber or other elastomeric material, and can provide themethod of sealing the cassette membrane against the cassette. Theseparate pump and valve control regions can be made of the samematerial, but with varying degrees of thickness or various profiles todeliver positive or negative pressure to the corresponding pump andvalve regions of the cassette membrane. The features are designed toform a tight seal between the cassette membrane and the actuationregions of the gasket, so that both outward and inward movement of thecontrol regions of the gasket are followed closely by the adjacentactuation portions of the cassette membrane. Opening and closing ofcassette valves, and filling and delivery strokes of the cassette pumpscan thus be performed effectively. The control gasket also serves toprotect the passageways of the pressure delivery block and the manifoldfrom fluid infiltration should any part of the membrane of an installedcassette fail or become torn or punctured. In medical applications, theinterposition of a gasket between the pressure source (air or fluid) andthe cassette provides an important safety feature that prevents theactuation fluid or air from being delivered to a cassette (and thenpossibly to a patient) if the cassette has a punctured or torn membrane.

The way in which the pump and valve control regions of the controlgasket are formed and shaped affects the efficiency of fluid pumping bythe cassette, and may also affect how accurately the system controllercan measure fluid flows in the cassette. The way in which the valvecontrol regions of the control gasket are formed may also affect howmuch noise or vibration is generated by the pumping system duringoperation. In the following description, an automated peritonealdialysis system is used as an example of the implementation thesefeatures, but the same principles and solutions can be applied to anyfluid handling device—medical or non-medical—that uses membrane-basedpump cassettes to move fluid.

SUMMARY

A fluid pumping system comprises a pumping cassette that comprises agenerally planar body having one or more depressions to form one or morepump chambers, a plurality of fluid flowpaths defined by rigid walls inthe body, and a plurality of valves comprising valve orifices defined byraised valve seats in the body. The pumping cassette has a flexiblemembrane affixed to a face of the body overlying the depressions,flowpaths and valve orifices. A base unit is arranged to receive thepumping cassette and to provide positive or negative pressure to theflexible membrane to operate the one or more pump chambers and theplurality of valves. A control gasket is positioned over a pressuredelivery block of the base unit, the control gasket having valve andpump control regions arranged to move toward or away from the pressuredelivery block under force of positive or negative pressure transmittedthrough passageways in the pressure delivery block. The valve controlregions are positioned adjacent corresponding valve control regions ofthe flexible membrane of the cassette, and opposite valve seats of theplurality of valves in the cassette. Portions of the control gasket notcomprising valve or pump control regions are arranged to provide asealing engagement of the flexible membrane against the rigid walls ofthe body, these portions of the control gasket lying in a plane of thecontrol gasket.

In an embodiment, the gasket has a first side configured for placementagainst a pressure delivery block and having an opposing second sideconfigured for placement against a flexible cassette membrane overlyingthe pump cassette, the gasket having a main body and an elastomericvalve actuation region that moves outward toward the cassette underpositive pressure and inward toward the pressure delivery block undernegative pressure. The valve actuation region is configured to bepositioned adjacent a valve actuation portion of the cassette membraneoverlying a cassette valve of the pump cassette. The valve actuationregion comprises a central portion configured to align with and to bepressed against a valve seat defining an orifice of the cassette valve;a peripheral portion configured to extend over a valve chamber of thepump cassette surrounding the valve orifice; and a vacuum channelforming a perimeter around at least a portion of the peripheral portionof the actuation region, the vacuum channel defined by an inner wallcontiguous with the peripheral portion of the actuation region, a floor,and an outer wall contiguous with or formed from the main body of thegasket, the vacuum channel being open to the second side of the gasket.The vacuum channel is fluidically connected to a vacuum port in thegasket that penetrates from the second side to the first side of thegasket, the vacuum port configured to communicate with a correspondingpressure delivery block vacuum port when the gasket is positionedagainst the pressure delivery block. And the inner wall of the vacuumchannel is configured to flex toward the pressure delivery block whenthe gasket valve actuation region is placed under negative pressure, atleast partially collapsing the inner wall of the vacuum channel whilethe valve actuation region moves inward and is pulled away from thecassette valve orifice when the pump cassette is present against thegasket.

The seat of the cassette valve seat may comprise a raisedcircumferential wall, and the gasket valve actuation region may beconfigured to press the cassette membrane against the circumferentialwall to occlude or close the cassette valve. The vacuum channel of thevalve actuation region may be configured to be positioned outside thecircumferential wall of the valve seat and over a well or chamber of thecassette valve. And the inner and outer walls of the vacuum channel maybe configured to apply pressure between the valve actuation region andthe valve seat when the first side of the valve actuation region isexposed to atmospheric pressure and the pump cassette is placed againstthe gasket.

In another embodiment, a fluid pumping system comprises a pump cassettecomprising a flexible membrane and a membrane based valve; a basepumping unit comprising a source of positive or negative pressure, apressure distribution manifold, and a pressure delivery block configuredto be positioned adjacent the cassette membrane and valve. A gasket isconfigured for placement between the pressure delivery block and thecassette membrane, a first side of the gasket positioned against thepressure delivery block and a second opposing side of the gasketpositioned against the cassette, the gasket comprising an elastomericvalve actuation region for positioning against the cassette membrane andvalve. The pressure delivery block comprises a control port fordelivering positive pressure to the valve actuation region to move thecassette membrane against a valve seat of the cassette valve, and fordelivering negative pressure to the valve actuation region to move thecassette membrane away from the valve seat of the cassette valve. Thegasket comprises a vacuum channel forming a perimeter around at least aportion of the valve actuation region, the vacuum channel defined by aninner wall contiguous with the valve actuation region, a floor, and anouter wall contiguous with or formed from a non-actuation region of thegasket surrounding the valve actuation region. The vacuum channel is incommunication with a vacuum port in the gasket that penetrates from thesecond side to the first side of the gasket and that is aligned with apressure delivery block vacuum port. And the inner wall of the vacuumchannel is configured to flex toward the pressure delivery block whennegative pressure is applied to the valve actuation region via thecontrol port, and patency of the vacuum channel is maintained.

The positive or negative pressure may be pneumatic pressure. The vacuumchannel may be positioned circumferentially around the periphery of thegasket valve actuation region. The cassette valve seat may comprise araised circumferential wall, and the gasket valve actuation region maybe configured to press the cassette membrane against the circumferentialwall to occlude or close the cassette valve. The vacuum channel of thevalve actuation region may be positioned outside the circumferentialwall of the valve seat and over a well or chamber of the cassette valve.And the inner and outer walls of the vacuum channel may be configured toapply pressure between the valve actuation region and the valve seatwhen the first side of the valve actuation region is exposed toatmospheric or ambient pressure,

In another embodiment, a method is disclosed of opening or closing apump cassette membrane valve comprising a flexible membrane overlying avalve seat of the pump cassette and using an elastomeric valve actuationregion of a gasket placed between the flexible membrane of the pumpcassette and a pressure delivery block. The method comprises: applyingnegative pressure via the pressure delivery block to an outer side ofthe gasket valve actuation region facing the cassette membrane via avacuum channel located along a periphery of the valve actuation regionand open to the outer side of the gasket valve actuation region;applying negative pressure via the pressure delivery block to an innerside of the gasket valve actuation region facing the pressure deliveryblock; flexing an outer wall of the vacuum channel toward the pressuredelivery block and away from pump cassette valve seat, the outer wallbeing contiguous with the valve actuation region of the gasket; andmaintaining patency of the vacuum channel so that the negative pressureapplied to the outer side of the gasket valve actuation region isuninterrupted.

Applying negative pressure may comprise applying negative pneumaticpressure. Applying negative pressure to an outer side of the gasketvalve actuation region may comprise delivering negative pressure via thevacuum channel circumferentially around the valve actuation region. Andthe method may further comprise closing the pump cassette membrane valveby applying positive pressure via the pressure delivery block to theinner side of the gasket valve actuation region against a raised wall ofthe valve seat surrounding an orifice of the pump cassette membranevalve.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic view of an automated peritoneal dialysis (APD)system that incorporates one or more aspects of the invention;

FIG. 1A shows an alternative arrangement for a dialysate delivery setshown in FIG. 1;

FIG. 2 is a schematic view of an illustrative set for use with the APDsystem of FIG. 1;

FIG. 3 is an exploded perspective view of a cassette in a firstembodiment;

FIG. 4 is a cross sectional view of the cassette along the line 4-4 inFIG. 3;

FIG. 5 is a perspective view of a vacuum mold that may be used to form amembrane having pre-formed pump chamber portions in an illustrativeembodiment;

FIG. 6 shows a front view of the cassette body of FIG. 3;

FIG. 7 is a front view of a cassette body including two different spacerarrangements in an illustrative embodiment;

FIG. 8 is a rear perspective view of the cassette body of FIG. 3;

FIG. 9 is a rear view of the cassette body of FIG. 3;

FIG. 10 is a perspective view of the APD system of FIG. 1 with the doorof the cycler in an open position;

FIG. 11 is a front view of a control surface of the cycler forinteraction with a cassette in the FIG. 10 embodiment;

FIG. 12 is a front view and selected cross-sectional views of anembodiment of a control surface of the cycler;

FIG. 13 is an exploded view of an assembly for the interface surface ofFIG. 90, with the mating pressure delivery block and pressuredistribution module;

FIG. 14 shows how the control gasket is interposed between the pressuredelivery block of the base unit and the pump cassette;

FIGS. 15A-C show cross-sectional views of the interaction between thecontrol gasket and a valve seat of the cassette, with views of thecassette membrane absent for clarity;

FIGS. 16A-B show cross-sectional views of the gasket perimeter vacuumchannel of FIGS. 15A-C and cassette membrane in a valve closed and valveopen position;

FIGS. 17A-B show cross-sectional views of an alternate gasket perimetervacuum channel arrangement in a valve closed and valve open position;

FIGS. 18A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region biased in aninverted position below the surface of the control gasket;

FIGS. 19A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region being biasedtoward the valve seat but not raised above the plane of the surface ofthe control gasket;

FIGS. 20A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region biased in aninverted position below the surface of the control gasket;

FIGS. 21A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region biased in aneutral position with respect to the surface of the control gasket;

FIGS. 22A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region being rippled ator below the surface of the control gasket;

FIGS. 23A-C show cross-sectional views of a cassette valve seat andgasket valve control region, the valve control region being rippled ator below the surface of the control gasket;

FIG. 24 is an exploded view of the integrated manifold;

FIG. 25 shows two isometric views of the integrated manifold;

FIG. 26 shows a schematic of the pneumatic system that controls fluidflow through the cycler;

FIG. 27 is a front side view of an embodiment of a cassette fixture;

FIG. 28 shows another example of a cassette fixture which is made from amodified cassette such as the cassette shown in FIG. 3;

FIG. 29 shows another example of a cassette fixture which is made from amodified cassette;

FIG. 30 is an exploded perspective view of an occluder in anillustrative embodiment;

FIG. 31 shows a pressure tracing from a control or actuation chamber ofa pumping cassette during a liquid delivery stroke; and

FIG. 32 is a perspective view of an interior section of the cycler ofFIG. 1 with the upper portion of the housing removed.

DETAILED DESCRIPTION

Automated Peritoneal Dialysis System

FIG. 1 shows an automated peritoneal dialysis (APD) system 10 thatencompasses one or more aspects of the invention. As shown in FIG. 1,for example, the system 10 in this illustrative embodiment includes adialysate delivery set 12 (which, in certain embodiments, can be adisposable set), a cycler 14 that interacts with the delivery set 12 topump liquid provided by a solution container 20 (e.g., a bag), and acontrol system 16 (e.g., including a programmed computer or other dataprocessor, computer memory, an interface to provide information to andreceive input from a user or other device, one or more sensors,actuators, relays, pneumatic pumps, tanks, a power supply, and/or othersuitable components—only a few buttons for receiving user control inputare shown in FIG. 1, but further details regarding the control systemcomponents are provided below) that governs the process to perform anAPD procedure. In this illustrative embodiment, the cycler 14 and thecontrol system 16 are associated with a common housing 82, but may beassociated with two or more housings and/or may be separate from eachother. The cycler 14 may have a compact footprint, suited for operationupon a table top or other relatively small surface normally found in thehome. The cycler 14 may be lightweight and portable, e.g., carried byhand via handles at opposite sides of the housing 82.

The set 12 in this embodiment is intended to be a single use, disposableitem, but instead may have one or more reusable components, or may bereusable in its entirety. The user associates the set 12 with the cycler14 before beginning each APD therapy session, e.g., by mounting acassette 24 within a front door 141 of the cycler 14, which interactswith the cassette 24 to pump and control fluid flow in the various linesof the set 12. For example, dialysate may be pumped both to and from thepatient to effect APD. Post therapy, the user may remove all or part ofthe components of the set 12 from the cycler 14.

As is known in the art, prior to use, the user may connect a patientline 34 of the set 12 to his/her indwelling peritoneal catheter (notshown) at a connection 36. In one embodiment, the cycler 14 may beconfigured to operate with one or more different types of cassettes 24,such as those having differently sized patient lines 34. For example,the cycler 14 may be arranged to operate with a first type of cassettewith a patient line 34 sized for use with an adult patient, and a secondtype of cassette with a patient line 34 sized for an infant or pediatricuse. The pediatric patient line 34 may be shorter and have a smallerinner diameter than the adult line so as to minimize the volume of theline, allowing for more controlled delivery of dialysate and helping toavoid returning a relatively large volume of used dialysate to thepediatric patient when the set 12 is used for consecutive drain and fillcycles. A heater bag 22, which is connected to the cassette 24 by a line26, may be placed on a heater container receiving portion (in this case,a tray) 142 of the cycler 14. The cycler 14 may pump fresh dialysate(via the cassette 24) into the heater bag 22 so that the dialysate maybe heated by the heater tray 142, e.g., by electric resistance heatingelements associated with the tray 142 to a temperature of about 37degrees C. Heated dialysate may be provided from the heater bag 22 tothe patient via the cassette 24 and the patient line 34. In analternative embodiment, the dialysate can be heated on its way to thepatient as it enters, or after it exits, the cassette 24 by passing thedialysate through tubing in contact with the heater tray 142, or throughan in-line fluid heater (which may be provided in the cassette 24). Useddialysate may be pumped from the patient via the patient line 34 to thecassette 24 and into a drain line 28, which may include one or moreclamps to control flow through one or more branches of the drain line28. In this illustrative embodiment, the drain line 28 may include aconnector 39 for connecting the drain line 28 to a dedicated drainreceptacle, and an effluent sample port 282 for taking a sample of useddialysate for testing or other analysis. The user may also mount thelines 30 of one or more containers 20 within the door 141. The lines 30may also be connected to a continuous or real-time dialysate preparationsystem. (The lines 26, 28, 30, 34 may include a flexible tubing and/orsuitable connectors and other components (such as pinch valves, etc.) asdesired.) The containers 20 may contain sterile peritoneal dialysissolution for infusion, or other materials (e.g., materials used by thecycler 14 to formulate dialysate by mixing with water, or admixingdifferent types of dialysate solutions). The lines 30 may be connectedto spikes 160 of the cassette 24, which are shown in FIG. 1 covered byremovable caps.

In one aspect of the invention, the cycler 14 may automatically removecaps from one or more spikes 160 of the cassette 24 and connect lines 30of solution containers 20 to respective spikes 160. This feature mayhelp reduce the possibility of infection or contamination by reducingthe chance of contact of non-sterile items with the spikes 160.

In another aspect, a dialysate delivery set 12 a may not have cassettespikes 160. Instead, one or more solution lines 30 may be permanentlyaffixed to the inlet ports of cassette 24, as shown in FIG. 1A. In thiscase, each solution line 30 may have a (capped) spike connector 35 formanual connection to a solution container or dialysate bag 20.

With various connections made, the control system 16 may pace the cycler14 through a series of fill, dwell, and/or drain cycles typical of anAPD procedure. For example, during a fill phase, the cycler 14 may pumpdialysate (by way of the cassette 24) from one or more containers 20 (orother source of dialysate supply) into the heater bag 22 for heating.Thereafter, the cycler 14 may infuse heated dialysate from the heaterbag 22 through the cassette 24 and into the patient's peritoneal cavityvia the patient line 34. Following a dwell phase, the cycler 14 mayinstitute a drain phase, during which the cycler 14 pumps used dialysatefrom the patient via the line 34 (again by way of the cassette 24), anddischarges spent dialysis solution into a nearby drain (not shown) viathe drain line 28.

The cycler 14 does not necessarily require the solution containers 20and/or the heater bag 22 to be positioned at a prescribed head heightabove the cycler 14, e.g., because the cycler 14 is not necessarily agravity flow system. Instead, the cycler 14 may emulate gravity flow, orotherwise suitably control flow of dialysate solution, even with thesource solution containers 20 above, below or at a same height as thecycler 14, with the patient above or below the cycler, etc. For example,the cycler 14 can emulate a fixed head height during a given procedure,or the cycler 14 can change the effective head height to either increaseor decrease pressure applied to the dialysate during a procedure. Thecycler 14 may also adjust the rate of flow of dialysate. In one aspectof the invention, the cycler 14 may adjust the pressure and/or flow rateof dialysate when provided to the patient or drawn from the patient soas to reduce the patient's sensation of the fill or drain operation.Such adjustment may occur during a single fill and/or drain cycle, ormay be adjusted across different fill and/or drain cycles. In oneembodiment, the cycler 14 may taper the pressure used to draw useddialysate from the patient near the end of a drain operation. Becausethe cycler 14 may establish an artificial head height, it may have theflexibility to interact with and adapt to the particular physiology orchanges in the relative elevation of the patient.

Cassette

In one aspect of the invention, a cassette 24 may include patient anddrain lines that are separately occludable with respect to solutionsupply lines. That is, safety critical flow to and from patient line maybe controlled, e.g., by pinching the lines to stop flow, without theneed to occlude flow through one or more solution supply lines. Thisfeature may allow for a simplified occluder device since occlusion maybe performed with respect to only two lines as opposed to occludingother lines that have little or no effect on patient safety. Forexample, in a circumstance where a patient or drain connection becomesdisconnected, the patient and drain lines may be occluded. However, thesolution supply and/or heater bag lines may remain open for flow,allowing the cycler 14 to prepare for a next dialysis cycle; e.g.,separate occlusion of patient and drain lines may help ensure patientsafety while permitting the cycler 14 to continue to pump dialysate fromone or more containers 20 to the heater bag 22 or to other solutioncontainers 20.

In another aspect of the invention, the cassette may have patient, drainand heater bag lines at one side or portion of the cassette and one ormore solution supply lines at another side or portion of the cassette,e.g., an opposite side of the cassette. Such an arrangement may allowfor separate occlusion of patient, drain or heater bag lines withrespect to solution lines as discussed above. Physically separating thelines attached to the cassette by type or function allows for moreefficient control of interaction with lines of a certain type orfunction. For example, such an arrangement may allow for a simplifiedoccluder design because less force is required to occlude one, two orthree of these lines than all lines leading to or away from thecassette. Alternately, this arrangement may allow for more effectiveautomated connection of solution supply lines to the cassette, asdiscussed in more detail below. That is, with solution supply lines andtheir respective connections located apart from patient, drain and/orheater bag lines, an automated de-capping and connection device mayremove caps from spikes on the cassette as well as caps on solutionsupply lines, and connect the lines to respective spikes withoutinterference by the patient, drain or heater bag lines.

FIG. 2 shows an illustrative embodiment of a cassette 24 thatincorporates aspects of the invention described above. In thisembodiment, the cassette 24 has a generally planar body and the heaterbag line 26, the drain line 28 and the patient line 34 are connected atrespective ports on the left end of the cassette body, while the rightend of the cassette body may include five spikes 160 to which solutionsupply lines 30 may be connected. In the arrangement shown in FIG. 2,each of the spikes 160 is covered by a spike cap 63, which may beremoved, exposing the respective spike and allowing connection to arespective line 30. As described above, the lines 30 may be attached toone or more solution containers or other sources of material, e.g., foruse in dialysis and/or the formulation of dialysate, or connected to oneor more collection bags for sampling purposes or for peritonealequilibration testing (PET test).

FIGS. 3 and 4 show exploded views (perspective and top views,respectively) of the cassette 24 in this illustrative embodiment. Thecassette 24 is formed as a relatively thin and flat member having agenerally planar shape, e.g., may include components that are molded,extruded or otherwise formed from a suitable plastic. In thisembodiment, the cassette 24 includes a base member 18 that functions asa frame or structural member for the cassette 24 as well as forming, atleast in part, various flow channels, ports, valve portions, etc. Thebase member 18 may be molded or otherwise formed from a suitable plasticor other material, such as a polymethyl methacrylate (PMMA) acrylic, ora cyclic olefin copolymer/ultra low density polyethylene (COC/ULDPE),and may be relatively rigid. In an embodiment, the ratio of COC to ULDPEcan be approximately 85%/15%. FIG. 3 also shows the ports for the heaterbag (port 150), drain (port 152) and the patient (port 154) that areformed in the base member 18. Each of these ports may be arranged in anysuitable way, such as, for example, a central tube 156 extending from anouter ring or skirt 158, or a central tube alone. Flexible tubing foreach of the heater bag, drain and patient lines 26, 28, 34 may beconnected to the central tube 156 and engaged by the outer ring 158, ifpresent.

Both sides of the base member 18 may be covered, at least in part, by amembrane 15 and 16, e.g., a flexible polymer film made from, forexample, polyvinyl chloride (PVC), that is cast, extruded or otherwiseformed. Alternatively, the sheet may be formed as a laminate of two ormore layers of poly-cyclohexylene dimethylene cyclohexanedicarboxylate(PCCE) and/or ULDPE, held together, for example, by a coextrudableadhesive (CXA). In some embodiments, the membrane thickness may be inthe range of approximately 0.002 to 0.020 inches thick. In a preferredembodiment, the thickness of a PVC-based membrane may be in the range ofapproximately 0.012 to 0.016 inches thick, and more preferablyapproximately 0.014 inches thick. In another preferred embodiment, suchas, for example, for laminate sheets, the thickness of the laminate maybe in the range of approximately 0.006 to 0.010 inches thick, and morepreferably approximately 0.008 inches thick.

Both membranes 15 and 16 may function not only to close or otherwiseform a part of flowpaths of the cassette 24, but also may be moved orotherwise manipulated to open/close valve ports and/or to function aspart of a pump diaphragm, septum or wall that moves fluid in thecassette 24. For example, the membranes 15 and 16 may be positioned onthe base member 18 and sealed (e.g., by heat, adhesive, ultrasonicwelding or other means) to a rim around the periphery of the base member18 to prevent fluid from leaking from the cassette 24. The membrane 15may also be bonded to other, inner walls of the base member 18, e.g.,those that form various channels, or may be pressed into sealing contactwith the walls and other features of the base member 18 when thecassette 24 suitably mounted in the cycler 14. Thus, both of themembranes 15 and 16 may be sealed to a peripheral rim of the base member18, e.g., to help prevent leaking of fluid from the cassette 24 upon itsremoval from the cycler 14 after use, yet be arranged to lie,unattached, over other portions of the base member 18. Once placed inthe cycler 14, the cassette 24 may be squeezed between opposed gasketsor other members so that the membranes 15 and 16 are pressed intosealing contact with the base member 18 at regions inside of theperiphery, thereby suitably sealing channels, valve ports, etc., fromeach other.

Other arrangements for the membranes 15 and 16 are possible. Forexample, the membrane 16 may be formed by a rigid sheet of material thatis bonded or otherwise made integral with the body 18. Thus, themembrane 16 need not necessarily be, or include, a flexible member.Similarly, the membrane 15 need not be flexible over its entire surface,but instead may include one or more flexible portions to permit pumpand/or valve operation, and one or more rigid portions, e.g., to closeflowpaths of the cassette 24. It is also possible that the cassette 24may not include the membrane 16 or the membrane 15, e.g., where thecycler 14 includes a suitable member to seal pathways of the cassette,control valve and pump function, etc.

In accordance with another aspect of the invention, the membrane 15 mayinclude a pump chamber portion 151 (“pump membrane”) that is formed tohave a shape that closely conforms to the shape of a corresponding pumpchamber 181 depression in the base 18. For example, the membrane 15 maybe generally formed as a flat member with thermoformed (or otherwiseformed) dome-like shapes 151 that conform to the pump chamberdepressions of the base member 18. The dome-like shape of the pre-formedpump chamber portions 151 may be constructed, for example, by heatingand forming the membrane over a vacuum form mold of the type shown inFIG. 5. As shown in FIG. 5, the vacuum may be applied through acollection of holes along the wall of the mold. Alternatively, the wallof the mold can be constructed of a porous gas-permeable material, whichmay result in a more uniformly smooth surface of the molded membrane. Inone example, the molded membrane sheet 15 is trimmed while attached tothe vacuum form mold. The vacuum form mold then presses the trimmedmembrane sheet 15 against the cassette body 18 and bonds them together.In one embodiment the membrane sheets 15, 16 are heat-welded to thecassette body 18. In this way, the membrane 15 may move relative to thepump chambers 181 to effect pumping action without requiring stretchingof the membrane 15 (or at least minimal stretching of the membrane 15),both when the membrane 15 is moved maximally into the pump chambers 181and (potentially) into contact with spacer elements 50 (e.g., as shownin solid line in FIG. 4 while pumping fluid out of the pump chamber181), and when the membrane 15 is maximally withdrawn from the pumpchamber 181 (e.g., as shown in dashed line in FIG. 4 when drawing fluidinto the pump chamber 181). Avoiding stretching of the membrane 15 mayhelp prevent pressure surges or other changes in fluid delivery pressuredue to sheet stretch and/or help simplify control of the pump whenseeking to minimize pressure variation during pump operation. Otherbenefits may be found, including reduced likelihood of membrane 15failure (e.g., due to tears in the membrane 15 resulting from stressesplace on the membrane 15 during stretching), and/or improved accuracy inpump delivery volume measurement, as described in more detail below. Inone embodiment, the pump chamber portions 151 may be formed to have asize (e.g., a define a volume) that is about 85-110% of the pump chamber181, e.g., if the pump chamber portions 151 define a volume that isabout 100% of the pump chamber volume, the pump chamber portion 151 maylie in the pump chamber 181 and in contact with the spacers 50 while atrest and without being stressed.

Providing greater control of the pressure used to generate a fill anddelivery stroke of liquid into and out of a pump chamber may haveseveral advantages. For example, it may be desirable to apply theminimum negative pressure possible when the pump chamber draws fluidfrom the patient's peritoneal cavity during a drain cycle. A patient mayexperience discomfort during the drain cycle of a treatment in partbecause of the negative pressure being applied by the pumps during afill stroke. The added control that a pre-formed membrane can provide tothe negative pressure being applied during a fill stroke may help toreduce the patient's discomfort.

A number of other benefits may be realized by using pump membranespre-formed to the contour of the cassette pump chamber. For example, theflow rate of liquid through the pump chamber can be made more uniform,because a constant pressure or vacuum can be applied throughout the pumpstroke, which in turn may simplify the process of regulating the heatingof the liquid. Moreover, temperature changes in the cassette pump mayhave a smaller effect on the dynamics of displacing the membrane, aswell as the accuracy of measuring pressures within the pump chambers. Inaddition, pressure spikes within the fluid lines can be minimized. Also,correlating the pressures measured by pressure transducers on thecontrol (e.g. pneumatic) side of the membrane with the actual pressureof the liquid on the pump chamber side of the membrane may be simpler.This in turn may permit more accurate head height measurements of thepatient and fluid source bags prior to therapy, improve the sensitivityof detecting air in the pump chamber, and improve the accuracy ofvolumetric measurements. Furthermore, eliminating the need to stretchthe membrane may allow for the construction and use of pump chambershaving greater volumes.

In this embodiment, the cassette 24 includes a pair of pump chambers 181that are formed in the base member 18, although one pump chamber or morethan two pump chambers are possible. In accordance with an aspect of theinvention, the inner wall of pump chambers 181 includes spacer elements50 that are spaced from each other and extend from the inner wall ofpump chamber 18 to help prevent portions of the membrane 15 fromcontacting the inner wall of pump chamber 181. (As shown on theright-side pump chamber 181 in FIG. 4, the inner wall is defined by sideportions 181 a and a bottom portion 181 b. The spacers 50 extendupwardly from the bottom portion 181 b in this embodiment, but couldextend from the side portions 181 a or be formed in other ways.) Bypreventing contact of the membrane 15 with the pump chamber inner wall,the spacer elements 50 may provide a dead space (or trap volume) whichmay help trap air or other gas in the pump chamber 181 and inhibit thegas from being pumped out of the pump chamber 181 in some circumstances.In other cases, the spacers 50 may help the gas move to an outlet of thepump chamber 181 so that the gas may be removed from the pump chamber181, e.g., during priming. Also, the spacers 50 may help prevent themembrane 15 from sticking to the pump chamber inner wall and/or allowflow to continue through the pump chamber 181, even if the membrane 15is pressed into contact with the spacer elements 50. In addition, thespacers 50 help to prevent premature closure of the outlet port of thepump chamber (openings 187 and/or 191) if the sheet happens to contactthe pump chamber inner wall in a non-uniform manner. Further detailsregarding the arrangement and/or function of spacers 50 are provided inU.S. Pat. Nos. 6,302,653 and 6,382,923, both of which are incorporatedherein by reference.

In this embodiment, the spacer elements 50 are arranged in a kind of“stadium seating” arrangement such that the spacer elements 50 arearranged in a concentric elliptical pattern with ends of the spacerelements 50 increasing in height from the bottom portion 181 b of theinner wall with distance away from the center of the pump chamber 181 toform a semi-elliptical domed shaped region (shown by dotted line in FIG.4). Positioning spacer elements 50 such that the ends of the spacerelements 50 form a semi-elliptical region that defines the domed regionintended to be swept by the pump chamber portion 151 of the membrane 15may allow for a desired volume of dead space that minimizes anyreduction to the intended stroke capacity of pump chambers 181. As canbe seen in FIG. 3 (and FIG. 6), the “stadium seating” arrangement inwhich spacer elements 50 are arranged may include “aisles” or breaks 50a in the elliptical pattern. Breaks (or aisles) 50 a help to maintain anequal gas level throughout the rows (voids or dead space) 50 b betweenspacer elements 50 as fluid is delivered from the pump chamber 181. Forexample, if the spacer elements 50 were arranged in the stadium seatingarrangement shown in FIG. 6 without breaks (or aisles) 50 a or othermeans of allowing liquid and air to flow between spacer elements 50, themembrane 15 might bottom out on the spacer element 50 located at theoutermost periphery of the pump chamber 181, trapping whatever gas orliquid is present in the void between this outermost spacer element 50and the side portions 181 a of the pump chamber wall. Similarly, if themembrane 15 bottomed out on any two adjacent spacer elements 50, any gasand liquid in the void between the elements 50 may become trapped. Insuch an arrangement, at the end of the pump stroke, air or other gas atthe center of pump chamber 181 could be delivered while liquid remainsin the outer rows. Supplying breaks (or aisles) 50 a or other means offluidic communication between the voids between spacer elements 50 helpsto maintain an equal gas level throughout the voids during the pumpstroke, such that air or other gas may be inhibited from leaving thepump chamber 181 unless the liquid volume has been substantiallydelivered.

In certain embodiments, spacer elements 50 and/or the membrane 15 may bearranged so that the membrane 15 generally does not wrap or otherwisedeform around individual spacers 50 when pressed into contact with them,or otherwise extend significantly into the voids between spacers 50.Such an arrangement may lessen any stretching or damage to membrane 15caused by wrapping or otherwise deforming around one or more individualspacer elements 50. For example, it has also been found to beadvantageous in this embodiment to make the size of the voids betweenspacers 50 approximately equal in width to the width of the spacers 50.This feature has shown to help prevent deformation of the membrane 15,e.g., sagging of the membrane into the voids between spacers 50, whenthe membrane 15 is forced into contact with the spacers 50 during apumping operation.

In accordance with another aspect of the invention, the inner wall ofpump chambers 181 may define a depression that is larger than the space,for example a semi-elliptical or domed space, intended to be swept bythe pump chamber portion 151 of the membrane 15. In such instances, oneor more spacer elements 50 may be positioned below the domed regionintended to be swept by the membrane portion 151 rather than extendinginto that domed region. In certain instances, the ends of spacerelements 50 may define the periphery of the domed region intended to beswept by the membrane 15. Positioning spacer elements 50 outside of, oradjacent to, the periphery of the domed region intended to be swept bythe membrane portion 151 may have a number of advantages. For example,positioning one or more spacer elements 50 such that the spacer elementsare outside of, or adjacent to, the domed region intended to be swept bythe flexible membrane provides a dead space between the spacers and themembrane, such as described above, while minimizing any reduction to theintended stroke capacity of pump chambers 181.

It should be understood that the spacer elements 50, if present, in apump chamber may be arranged in any other suitable way, such as forexample, shown in FIG. 7. The left side pump chamber 181 in FIG. 7includes spacers 50 arranged similarly to that in FIG. 6, but there isonly one break or aisle 50 a that runs vertically through theapproximate center of the pump chamber 181. The spacers 50 may bearranged to define a concave shape similar to that in FIG. 6 (i.e., thetops of the spacers 50 may form the semi-elliptical shape shown in FIGS.3 and 4), or may be arranged in other suitable ways, such as to form aspherical shape, a box-like shape, and so on. The right-side pumpchamber 181 in FIG. 7 shows an embodiment in which the spacers 50 arearranged vertically with voids 50 b between spacers 50 also arrangedvertically. As with the left-side pump chamber, the spacers 50 in theright-side pump chamber 181 may define a semi-elliptical, spherical,box-like or any other suitably shaped depression. It should beunderstood, however, that the spacer elements 50 may have a fixedheight, a different spatial pattern than those shown, and so on.

Also, the membrane 15 may itself have spacer elements or other features,such as ribs, bumps, tabs, grooves, channels, etc., in addition to, orin place of the spacer elements 50. Such features on the membrane 15 mayhelp prevent sticking of the membrane 15, etc., and/or provide otherfeatures, such as helping to control how the sheet folds or otherwisedeforms when moving during pumping action. For example, bumps or otherfeatures on the membrane 15 may help the sheet to deform consistentlyand avoid folding at the same area(s) during repeated cycles. Folding ofa same area of the membrane 15 at repeated cycles may cause the membrane15 to prematurely fail at the fold area, and thus features on themembrane 15 may help control the way in which folds occur and where.

In this illustrative embodiment, the base member 18 of the cassette 24defines a plurality of controllable valve features, fluid pathways andother structures to guide the movement of fluid in the cassette 24. FIG.6 shows a plan view of the pump chamber side of the base member 18,which is also seen in perspective view in FIG. 3. FIG. 8 shows aperspective view of a back side of the base member 18, and FIG. 9 showsa plan view of the back side of the base member 18. The tube 156 foreach of the ports 150, 152 and 154 fluidly communicates with arespective valve well or chamber 183 that is formed in the base member18. The valve wells or chambers 183 are fluidly isolated from each otherby walls surrounding each valve well or chamber 183 and by sealingengagement of the membrane 15 with the walls around the wells orchambers 183. Similarly, valve wells 185 can be sealed from ports 186 byoperation of the cassette membrane 15. And pump inlet or outlet valveshave wells 189, 194 that can be sealed from ports 190, 192. As mentionedabove, the membrane 15 may sealingly engage the walls 196 (which formthe valve seats) around each valve well or chamber 183, 185, 189 and 194(and other walls of the base member 18) by being pressed into contactwith the walls, e.g., when loaded into the cycler 14. Fluid in the valvewells or chambers 183, 185, 189 and 194 may flow into or out of arespective valve port or orifice 184, 186, 190 and 192, if the membrane15 is not pressed into sealing engagement with the valve port or orifice184, etc. Thus, each valve port or orifice 184 defines a valve (e.g., a“volcano valve”) that can be opened and closed by selectively moving aportion of the membrane 15 associated with the valve port or orifice184. The cassette valve port or orifice seat can be defined by a raisedcircumferential wall 196, forming a valve seat (see, e.g., FIGS. 3, 4),so that occlusion of the port by the cassette membrane 15 and associatedvalve control region of gasket 148 can be achieved more reliably. But inother embodiments, a cassette valve port seat may not comprise a raisedwall 196 if the cassette membrane 15 is sufficiently flexible orappropriately shaped, and the applied pressure is sufficient to seal thevalve port 184 from the valve well or chamber 183.

As will be described in more detail below, the cycler 14 may selectivelycontrol the position of portions of the membrane 15 so that cassettevalve ports or orifices (such as ports 184) may be opened or closed soas to control flow through the various fluid channels and other pathwaysin the cassette 24. Flow through the valve ports or orifices 184 leadsto the back side of the base member 18. For the valve ports 184associated with the heater bag and the drain (ports 150 and 152), thevalve ports 184 lead to a common channel 200 formed at the back side ofthe base member 18. As with the valve wells or chambers 183, the channel200 is isolated from other channels and pathways of the cassette 24 bythe sheet 16 making sealing contact with the walls of the base member 18that form the channel 200. For the valve port or orifice 184 associatedwith the patient line port 154, flow through the port 184 leads to acommon channel 202 on the back side of the base member 18. Commonchannel 200 may also be referred to herein as an upper fluidic bus andcommon channel 202 may also be referred to herein as a lower fluidicbus.

Returning to FIG. 6, each of the spikes 160 (shown uncapped in FIG. 6)fluidly communicates with a respective valve well 185, which areisolated from each other by walls and sealing engagement of the membrane15 with the walls that form the wells 185. Fluid in the valve wells 185may flow into a respective valve port 186, if the membrane 15 is not insealing engagement with the port 186. (Again, the position of portionsof the membrane 15 over each valve port 186 can be controlled by thecycler 14 to open and close the valve ports 186.) Flow through the valveports 186 leads to the back side of the base member 18 and into thecommon channel 202. Thus, in accordance with one aspect of theinvention, a cassette may have a plurality of solution supply lines (orother lines that provide materials for providing dialysate) that areconnected to a common manifold or channel of the cassette, and each linemay have a corresponding valve to control flow from/to the line withrespect to the common manifold or channel. Fluid in the channel 202 mayflow into lower openings 187 of the pump chambers 181 by way of openings188 that lead to lower pump valve wells 189 (see FIG. 6). Flow from thelower pump valve wells 189 may pass through a respective lower pumpvalve port 190 if a respective portion of the membrane 15 is not pressedin sealing engagement with the port 190. As can be seen in FIG. 9, thelower pump valve ports 190 lead to a channel that communicates with thelower openings 187 of the pump chambers 181. Flow out of the pumpchambers 181 may pass through the upper openings 191 and into a channelthat communicates with an upper valve port 192. Flow from the uppervalve port 192 (if the membrane 15 is not in sealing engagement with theport 192) may pass into a respective upper valve well 194 and into anopening 193 that communicates with the common channel 200 on the backside of the base member 18.

As will be appreciated, the cassette 24 may be controlled so that thepump chambers 181 can pump fluid from and/or into any of the ports 150,152 and 154 and/or any of the spikes 160. For example, fresh dialysateprovided by one of the containers 20 that is connected by a line 30 toone of the spikes 160 may be drawn into the common channel 202 byopening the appropriate valve port 186 for the proper spike 160 (andpossibly closing other valve ports 186 for other spikes). Also, thelower pump valve ports 190 may be opened and the upper pump valve ports192 may be closed. Thereafter, the portion of the membrane 15 associatedwith the pump chambers 181 (i.e., pump membranes 151) may be moved(e.g., away from the base member 18 and the pump chamber inner wall) soas to lower the pressure in the pump chambers 181, thereby drawing fluidin through the selected spike 160 through the corresponding valve port186, into the common channel 202, through the openings 188 and into thelower pump valve wells 189, through the (open) lower pump valve ports190 and into the pump chambers 181 through the lower openings 187. Thevalve ports 186 are independently operable, allowing for the option todraw fluid through any one or a combination of spikes 160 and associatedsource containers 20, in any desired sequence, or simultaneously. (Ofcourse, only one pump chamber 181 need be operable to draw fluid intoitself. The other pump chamber may be left inoperable and closed off toflow by closing the appropriate lower pump valve port 190.)

With fluid in the pump chambers 181, the lower pump valve ports 190 maybe closed, and the upper pump valve ports 192 opened. When the membrane15 is moved toward the base member 18, the pressure in the pump chambers181 may rise, causing fluid in the pump chambers 181 to pass through theupper openings 191, through the (open) upper pump valve ports 192 andinto the upper pump valve wells 194, through the openings 193 and intothe common channel 200. Fluid in the channel 200 may be routed to theheater bag port 150 and/or the drain port 152 (and into thecorresponding heater bag line or drain line) by opening the appropriatevalve port 184. In this way, for example, fluid in one or more of thecontainers 20 may be drawn into the cassette 24, and pumped out to theheater bag 22 and/or the drain.

Fluid in the heater bag 22 (e.g., after having been suitably heated onthe heater tray for introduction into the patient) may be drawn into thecassette 24 by opening the valve port 184 for the heater bag port 150,closing the lower pump valve ports 190, and opening the upper pump valveports 192. By moving the portions of the membrane 15 associated with thepump chambers 181 away from the base member 18, the pressure in the pumpchambers 181 may be lowered, causing fluid flow from the heater bag 22and into the pump chambers 181. With the pump chambers 181 filled withheated fluid from the heater bag 22, the upper pump valve ports 192 maybe closed and the lower pump valve ports 190 opened. To route the heateddialysate to the patient, the valve port 184 for the patient port 154may be opened and valve ports 186 for the spikes 160 closed. Movement ofthe membrane 15 in the pump chambers 181 toward the base member 18 mayraise the pressure in the pump chambers 181 causing fluid to flowthrough the lower pump valve ports 190, through the openings 188 andinto the common channel 202 to, and through, the (open) valve port 184for the patient port 154. This operation may be repeated a suitablenumber of times to transfer a desired volume of heated dialysate to thepatient.

When draining the patient, the valve port 184 for the patient port 154may be opened, the upper pump valve ports 192 closed, and the lower pumpvalve ports 190 opened (with the spike valve ports 186 closed). Themembrane 15 may be moved to draw fluid from the patient port 154 andinto the pump chambers 181. Thereafter, the lower pump valve ports 190may be closed, the upper valve ports 192 opened, and the valve port 184for the drain port 152 opened. Fluid from the pump chambers 181 may thenbe pumped into the drain line for disposal or for sampling into a drainor collection container. (Alternatively, fluid may also be routed to oneor more spikes 160/lines 30 for sampling or drain purposes). Thisoperation may be repeated until sufficient dialysate is removed from thepatient and pumped to the drain.

The heater bag 22 may also serve as a mixing container. Depending on thespecific treatment requirements for an individual patient, dialysate orother solutions having different compositions can be connected to thecassette 24 via suitable solution lines 30 and spikes 160. Measuredquantities of each solution can be added to heater bag 22 using cassette24, and admixed according to one or more pre-determined formulae storedin microprocessor memory and accessible by control system 16.Alternatively, specific treatment parameters can be entered by the uservia user interface 144. The control system 16 can be programmed tocompute the proper admixture requirements based on the type of dialysateor solution containers connected to spikes 160, and can then control theadmixture and delivery of the prescribed mixture to the patient.

In accordance with an aspect of the invention, the pressure applied bythe pumps to dialysate that is infused into the patient or removed fromthe patient may be controlled so that patient sensations of “tugging” or“pulling” resulting from pressure variations during drain and filloperations may be minimized. For example, when draining dialysate, thesuction pressure (or vacuum/negative pressure) may be reduced near theend of the drain process, thereby minimizing patient sensation ofdialysate removal. A similar approach may be used when nearing the endof a fill operation, i.e., the delivery pressure (or positive pressure)may be reduced near the end of fill. Different pressure profiles may beused for different fill and/or drain cycles in case the patient is foundto be more or less sensitive to fluid movement during different cyclesof the therapy. For example, a relatively higher (or lower) pressure maybe used during fill and/or drain cycles when a patient is asleep, ascompared to when the patient is awake. The cycler 14 may detect thepatient's sleep/awake state, e.g., using an infrared motion detector andinferring sleep if patient motion is reduced, or using a detected changein blood pressure, brain waves, or other parameter that is indicative ofsleep, and so on. Alternately, the cycler 14 may simply “ask” thepatient—“are you asleep?” and control system operation based on thepatient's response (or lack of response).

Set Loading and Operation

FIG. 10 shows a perspective view of the APD system 10 of FIG. 1 with thedoor 141 of the cycler 14 lowered into an open position, exposing amounting location 145 for the cassette 24 and a carriage 146 for thesolution lines 30. (In this embodiment, the door 141 is mounted by ahinge at a lower part of the door 141 to the cycler housing 82.) Whenloading the set 12, the cassette 24 is placed in the mounting location145 with the membrane 15 and the pump chamber side of the cassette 24facing upwardly, allowing the portions of the membrane 15 associatedwith the pump chambers and the valve ports to interact with a controlsurface or gasket 148 of the cycler 14 when the door 141 is closed. Themounting location 145 may be shaped so as to match the shape of the basemember 18, thereby ensuring proper orientation of the cassette 24 in themounting location 145. In this illustrative embodiment, the cassette 24and mounting location 145 have a generally rectangular shape with asingle larger radius corner which requires the user to place thecassette 24 in a proper orientation into the mounting location 145 orthe door 141 will not close. It should be understood, however, thatother shapes or orientation features for the cassette 24 and/or themounting location 145 are possible.

In accordance with an aspect of the invention, when the cassette 24 isplaced in the mounting location 145, the patient, drain and heater baglines 34, 28 and 26 are routed through a channel 40 in the door 141 tothe left as shown in FIG. 37. The channel 40, which may include guides41 or other features, may hold the patient, drain and heater bag lines34, 28 and 26 so that an occluder 147 may selectively close/open thelines for flow. Upon closing of door 141, occluder 147 can compress oneor more of patient, drain and heater bag lines 34, 28 and 26 againstoccluder stop 29. Generally, the occluder 147 may allow flow through thelines 34, 28 and 26 when the cycler 14 is operating (and operatingproperly), yet occlude the lines when the cycler 14 is powered down(and/or not operating properly). Occlusion of the lines may be performedby pressing on the lines, or otherwise pinching the lines to close offthe flow path in the lines. Preferably, the occluder 147 may selectivelyocclude at least the patient and drain lines 34 and 28.

When the cassette 24 is mounted and the door 141 is closed, the pumpchamber side of the cassette 24 and the membrane 15 may be pressed intocontact with the control surface or gasket 148, e.g., by an air bladder,spring or other suitable arrangement in the door 141 behind the mountinglocation 145 that squeezes the cassette 24 between the mounting location145 and the control surface 148. This containment of the cassette 24 maypress the membranes 15 and 16 into contact with walls and other featuresof the base member 18, thereby isolating channels and other flow pathsof the cassette 24 as desired. The control surface or gasket 148 mayinclude a flexible or elastomeric material, e.g., a sheet of siliconerubber or other material, either involving the entire gasket, or atleast portions of the gasket that serve as pump or valve controlregions. The gasket is positioned adjacent the membrane 15 and canselectively move portions of the membrane 15 to cause pumping action inthe pump chambers 181 and opening/closing of valve ports of the cassette24. The control gasket 148 may be associated with the various portionsof the membrane 15, e.g., placed into intimate contact with each other,so that portions of the membrane 15 move in response to movement ofcorresponding portions of the control gasket 148. For example, themembrane 15 and control gasket 148 may be positioned close together, anda suitable vacuum (or pressure that is lower relative to ambient) may beintroduced through vacuum ports suitably located in the control gasket148 (preferably near the respective pump and valve control regions toevacuate air from between the gasket and cassette membrane specificallyin the control regions) A negative pressure is maintained between themembrane 15 and the control gasket 148 so that the membrane 15 and thecontrol gasket 148 are essentially stuck together, at least in regionsof the membrane 15 that require movement to open/close valve portsand/or to cause pumping action. In another embodiment, the membrane 15and control gasket 148 may be adhered together, or otherwise suitablyassociated.

In some embodiments, the surface of the control gasket 148 facing thecorresponding cassette membrane overlying the pump chambers and/orvalves is textured or roughened. The texturing creates a plurality ofsmall passages horizontally or tangentially along the surface of thegasket when the gasket is pulled against the surface of thecorresponding cassette membrane. This may improve evacuation of airbetween the gasket surface and the cassette membrane surface in thetextured locations. It may also improve the accuracy of pump chambervolume determinations using pressure-volume relationships (such as, forexample, ideal gas law calculations), by minimizing trapped pockets ofair between the gasket and the membrane. It may also improve thedetection of any liquid that may leak into the potential space betweenthe gasket and the cassette membrane. In an embodiment, the texturingmay be accomplished by masking the portions of the gasket mold that donot form the portions of the gasket corresponding to the pump membraneand valve membrane locations. A chemical engraving process such as theMOLD-TECH® texturing and chemical engraving process may then be appliedto the unmasked portions of the gasket mold. Texturing may also beaccomplished by any of a number of other processes, such as, forexample, sand blasting, laser etching, or utilizing a mold manufacturingprocess using electrical discharge machining.

FIG. 11 shows a plan view of the control gasket 148 of the cycler 14that interacts with the pump chamber side of the cassette 24 (e.g.,shown in FIG. 6) to cause fluid pumping and flow path control in thecassette 24. When at rest, the control gasket 148, which may bedescribed as a type of gasket, and comprise a sheet of silicone rubber,may be generally flat. Valve control regions 1481 may (or may not) bedefined in the control gasket 148, e.g., by a scoring, groove, rib orother feature in or on the sheet surface, and be arranged to be movableor elastically deformable/stretchable in a direction generallytransverse to the plane of the sheet. By moving inwardly/outwardly, thevalve control regions 1481 can move associated portions of the membrane15 on the cassette 24 so as to open and close respective valve ports184, 186, 190 and 192 of the cassette 24, and thus control flow in thecassette 24. Two larger regions, pump control regions 1482, may likewisebe movable so as to move associated shaped portions 151 of the membrane15 that cooperate with the pump chambers 181. Like the shaped portions151 of the membrane 15, the pump control regions 1482 may be shaped in away to correspond to the shape of the pump chambers 181 when the controlregions 1482 are extended into the pump chambers 181. In this way, theportion of the control sheet or gasket 148 at the pump control regions1482 need not necessarily be stretched or otherwise resiliently deformedduring pumping operation.

Typically, the control gasket 148 is constructed from a single material,so that it can be readily formed from a mold. The flat portions of thegasket help to compress and seal the cassette membrane 15 against theborder or perimeter walls of the cassette, sealing liquid flowpathswithin the cassette when it is pressed against the controlsurface/gasket and its supporting mating block 170. Similarly, as thecassette is pressed against the control surface/gasket, the fluidcontrol ports 173A, 173C can be sealed from each other, so that thecontrol chambers 171A, and 2746 can be individually and independentlypressurized with positive or negative pneumatic pressure.

Alternatively, the movable portions of the control gasket 148, such asthe pump control regions 1482 and valve control regions 1481 maycomprise a material with different thickness, elasticity and/ordurometer values than the flat portions of the gasket. The differentmaterials can be fused together in a molding or overmolding operation,or can be solvent-bonded together, for example, using an adhesive. Thepump control regions 1482 and valve control regions 1482 of the gasket148 preferably are constructed of elastomeric material of a thicknessand elasticity to permit their adequate movement in response to positiveor negative actuation pressure, in order to move the associated pump andvalve portions of the cassette membrane 15 a desired amount. The valvecontrol regions 1482 in particular benefit from a relatively stiffcontrol gasket body adjacent the periphery of the valve control regions,so that it can contribute to supporting the body of the valve controlregion against the valve ports of the cassette when in a valve closingposition.

Each of the regions 1481 and 1482 may have an associated vacuum orevacuation port 1483 that may be used to remove all or substantially allof any air or other fluid that may be present between the membrane 15 ofcassette 24, and the control gasket 148 of cycler 14, e.g., after thecassette 24 is loaded into the cycler 14 and the door 141 closed. Thismay help ensure close contact of the membrane 15 with the controlregions 1481 and 1482, and help control the delivery of desired volumeswith pump operation and/or the open/closed state of the various valveports. Note that the vacuum ports 1482 are formed in locations where thecontrol gasket 148 will not be pressed into contact with a wall or otherrelatively rigid feature of the cassette 24. For example, in accordancewith one aspect of the invention, one or both of the pump chambers ofthe cassette 24 may include a vacuum vent clearance region formedadjacent the pump chamber. In this illustrative embodiment as shown inFIGS. 3 and 6, the base member 18 may include vacuum vent port clearanceor extension features 182 (e.g., recessed areas that are fluidlyconnected to the pump chambers) adjacent and outside the oval-shapeddepressions forming the pump chambers 181 to allow the vacuum vent port1483 for the pump control region 1482 to remove any air or fluid frombetween membrane 15 and control gasket 148 (e.g., due to rupture of themembrane 15) without obstruction. The extension feature may also belocated within the perimeter of pump chamber 181. However, locating ventport feature 182 outside the perimeter of pump chamber 181 may preservemore of the pumping chamber volume for pumping liquids, e.g., allows forthe full footprint of pump chamber 181 to be used for pumping dialysate.Preferably, extension feature 182 is located in a vertically lowerposition in relation to pump chamber 181, so that any liquid that leaksbetween membrane 15 and control gasket 148 is drawn out through vacuumport 1483 at the earliest opportunity. Similarly, vacuum ports 1483associated with valves 1481 are preferably located in a verticallyinferior position with respect to valves 1481.

In some embodiments, the surface of the control gasket 148 or gasketfacing the corresponding cassette membrane overlying the pump chambersand/or valves is textured or roughened. The texturing creates aplurality of small passages horizontally or tangentially along thesurface of the gasket when the gasket is pulled against the surface ofthe corresponding cassette membrane. This may improve evacuation of airbetween the gasket surface and the cassette membrane surface in thetextured locations. It may also improve the accuracy of pump chambervolume determinations using pressure-volume relationships (such as, forexample, in the FMS procedures described elsewhere), by minimizingtrapped pockets of air between the gasket and the membrane. It may alsoimprove the detection of any liquid that may leak into the potentialspace between the gasket and the cassette membrane. In an embodiment,the texturing may be accomplished by masking the portions of the gasketmold that do not form the portions of the gasket corresponding to thepump membrane and valve membrane locations. A chemical engraving processsuch as the MOLD-TECH® texturing and chemical engraving process may thenbe applied to the unmasked portions of the gasket mold. Texturing mayalso be accomplished by any of a number of other processes, such as, forexample, sand blasting, laser etching, or utilizing a mold manufacturingprocess using electrical discharge machining.

FIG. 12 shows that control gasket 148 may optionally be constructed ormolded to have a rounded transition between the base element 1480 ofcontrol gasket 148 and the actuation portions of its valve and pumpcontrol regions 1481, 1482. These junctions or channels 1491 and 1492may be molded with a small radius to transition from base element 1480to valve control region 1481 and pump control region 1482, respectively.A rounded or smooth transition helps to prevent premature fatigue andfracture of the material comprising control gasket 148, and may improveits longevity. In an optional embodiment, radial channels 1484 lead fromvacuum ports 1483 to the pump control regions 1482 and valve controlregions 1481, and may need to be lengthened somewhat to accommodate thetransition feature. Junctions or channels 1491 and 1492 function asvacuum channels, transmitting and distributing the vacuum being appliedthrough the pressure delivery block to the potential spaces between thepump control regions 1482 and valve control regions 1481 and thecorresponding pump and valve portions of the cassette membrane 15. (Notethat these vacuum channels optionally may also be used to transmitpositive pressure to the potential spaces between gasket control regionsand the corresponding cassette membrane regions in order to aid inseparating the cassette from the pressure delivery block when desired).The vacuum channels 1491 and 1492 run along the periphery or perimeterof the pump or valve control regions of the gasket 148, and allow a moreuniform application of vacuum to these surfaces.

Although not necessarily required, these vacuum channels 1491 and 1492may optionally and conveniently extend along the circumference of theperiphery of the pump and valve control regions of gasket 148, as shown,for example, in FIG. 12. For either a pump control region 1482 or avalve control region 1481 of the gasket 148, the channel 1484corresponding to a particular control region is radially oriented toconnect a nearby gasket vacuum port 1483 to channel 1491 or 1492 thatextends along a perimeter of its associated gasket control region.Although the vacuum channel 1491, 1492 need not completely encircle itsassociated pump or valve control region to ensure uniform application ofvacuum to the entire surface of the control region, a circumferentialarrangement also serves the purpose of providing a flexible mechanicaltransition between the base element 1480 of gasket 148 and the body ofthe gasket control region 1481 or 1482.

The control regions 1481 and 1482 may be moved or elastically deformedby controlling a pneumatic pressure and/or volume on a side of thecontrol gasket 148 opposite the cassette 24, e.g., on a back side of theelastomeric sheet that forms the control gasket 148. For example, asshown in FIGS. 15A-23C, the control gasket 148 may be backed by a matingor pressure delivery block 170 that includes control chambers ordepressions 171A located in association with each control region 1481,and control chambers or depressions 171B, located in association witheach control region 1482, and that are isolated from each other (or atleast can be controlled independently of each other if desired). Thecontrol chambers or depressions 171A may define a volume. The surface ofmating or pressure delivery block 170 forms a mating interface withcassette 24 when cassette 24 is pressed into operative association withcontrol gasket 148 backed by mating block 170 (see, e.g., FIGS. 13, 14).The control chambers or depressions of mating block 170 are thus coupledto complementary valve or pumping chambers of cassette 24, sandwichingthe control regions 1481 and 1482 of control gasket 148 between matingblock 170 and the associated regions of cassette membrane 15 (such asshaped portion 151) adjacent to cassette 24. Positively or negativelypressurized air or other control fluid may be moved into or out of thecontrol chambers or depressions 171A, 171B of mating block 170 for theregions 1481, 1482, thereby moving the control regions 1481, 1482 asdesired to open/close valve ports of the cassette 24 and/or effectpumping action at the pump chambers 181. In one illustrative embodimentshown in FIGS. 15A-C, the control chambers 171A may be arranged ascylindrically-shaped regions or recesses backing each of the valvecontrol regions 1481 of gasket 148. In one configuration of the valvecontrol region 1481 of the gasket 148, the surface of the control regionis slightly elevated above the overall surface of the gasket, biasingthe elastically deformable control region toward the corresponding valveseat 184 of the cassette. Thus, positive pneumatic pressure appliedagainst the valve control region is more likely to reliably seal thecassette membrane 15 against the valve seat 184. On the other hand, atleast a portion of the negative pressure applied to the valve controlregion to lift the adjacent cassette membrane 15 off the valve seat mustbe expended to overcome the outwardly biased valve control region of thecontrol gasket 148. It is also apparent that when the gasket is placedagainst the underlying mating block 170, a space 1478 under the dome ofthe control region 1481 combines with the control chamber 171A to becomethe total control volume that is pressurized positively or negatively tomove the control region 1481 toward or away from the valve seat. Theamount of total control volume that needs to be pressurized will varybased on the shape and configuration of the valve control region of thegasket (e.g., convex vs. concave toward the cassette).

The control chambers or depressions 171B may comprise ellipsoid, ovoidor hemi-spheroid voids or depressions backing the pump control regions1482. Fluid control ports 173A may be provided for each control chamber171A so that the cycler 14 can control the volume of fluid and/or thepressure of fluid in each of the valve control chambers 1481. Fluidcontrol ports 173C may be provided for each control chamber 171B so thatthe cycler 14 can control the volume of fluid and/or the pressure offluid in each of the volume control chambers 1482. For example, as shownin FIG. 13, the mating block 170 may be mated with a manifold 172 thatincludes various ports, channels, openings, voids and/or other featuresthat communicate with the control chambers 171A, B and allow suitablepneumatic pressure/vacuum to be applied to the control chambers 171A, B.Although not shown, control of the pneumatic pressure/vacuum may beperformed in any suitable way, such as through the use of controllablevalves, pumps, pressure sensors, accumulators, and so on. Of course, itshould be understood that the control regions 1481, 1482 may be moved inother ways, such as by gravity-based systems, hydraulic systems, and/ormechanical systems (such as by linear motors, etc.), or by a combinationof systems including pneumatic, hydraulic, gravity-based and mechanicalsystems.

Gasket Vacuum Channels

In order to function optimally, the perimeter vacuum channels 1491 or1492 should remain patent throughout the range of motion of the gasketpump control 1482 or valve control 1481 regions during operation of thecassette (i.e. during application of positive or negative pressurethrough the valve control ports 173A or pump control ports 173C). Thatway, a continuous negative pressure can be transmitted to the potentialspace between the cassette membrane and gasket control region, andmovement of the adjacent cassette membrane 15 can more closely followthe movement of the pump and valve control regions of the gasket.(Depending on the amount of negative pressure applied through the vacuumport and channels, an inter-membrane space may nevertheless develop atthe point when maximal negative pressure is being applied to the valvecontrol region to open a valve, as shown in FIGS. 16 and 17). To ensurea patent vacuum channel 1491, previous versions of the gasket 148 wereconstructed to have both walls of the perimeter channel sufficientlyrigid not to flex or collapse away when negative pressure is applied tothe valve control region 1481 of the gasket 148. Previous perimeterchannels were therefore constructed with this rigidity constraint. Anexample of prior perimeter vacuum channels is shown in FIGS. 15A-C. Inthis example, vacuum channel 1491 has a semi-circular cross-sectionalprofile concave to an opposing cassette or cassette membrane (see FIG.15B). In this case, the gasket valve control surface 1481 has a slightlyconvex shape toward the cassette or cassette membrane. Thisconfiguration favors the effective closure of the associated cassettevalve, because the gasket valve control region is biased toward closureand the vacuum channel is defined by supporting walls that exhibitminimal flexing away from the cassette valve during delivery of negativepressure to the valve control port 173A.

The degree of valve opening in the prior version of the gasket valvecontrol region is shown in FIGS. 16A-B. FIG. 16A shows an example of theposition of the gasket valve control region 1481 and the associatedcassette membrane 15 against the wall or seat 196 of cassette valve port184. Depending on the type of valve control region configuration, thismay correspond to a closed valve position under both positive pressureand under ambient (eg., atmospheric) pressure conditions, indicatingthat the gasket valve control region is biased against the cassette port184. However, the configuration under negative pressure may result in asub-optimal valve opening area 400 as shown in FIG. 16B. This may resultis fluid flow rates through the cassette valve that are sub-optimal, andmay also generate membrane vibrations leading to unwanted noise.

A new configuration of the gasket valve control region 1481 has beendeveloped to reach a more useful compromise between the need to maintainan open vacuum channel 1491, to achieve reliable closure of the cassettevalve, and to achieve a greater opening area of the cassette valve whenthe gasket valve control region is placed under negative pressure. Thisis shown in FIGS. 17A-B. In this case, an outer wall 1493 of the vacuumchannel, contiguous with or comprising the body of the gasket 148outside of the valve control region 1481, is designed to remainrelatively stiff, so that it does not collapse or flex to the point ofobliterating the vacuum channel 1491. Also defining the vacuum channel1491 is a floor 1490, and is an inner wall 1495 contiguous with acontact portion 1497 of the gasket valve control region 1481. Thecontact portion 1497 comprises that portion of the gasket valve controlregion 1481 that is adjacent the portion of the cassette membrane 15that contacts the cassette valve port wall or seat 196 to seal the portfrom the valve well or chamber 183. In this embodiment, the inner vacuumchannel wall 1495 is designed, constructed or molded to have greaterflexibility than the outer wall 1493, so that it is able to flex orpartially collapse away from the cassette when the gasket valve controlregion 1481 is placed under negative pressure to open the cassettevalve. The patency of the vacuum channel 1491 is preserved to an extentsufficient to maintain continuous vacuum pressure through all phases ofthe operation of the cassette valve. An example of this property isshown in FIG. 17B. The valve opening area 402 is greater than the priorversion of the gasket 148 shown in FIGS. 16A-B, which improves fluidflow rates through the cassette valve and reduces flow-related noise. Inone embodiment, the elastomeric property of the inner wall 1495 isdifferent from that of the outer wall 1493. Preferably, formanufacturing simplicity, the difference in the elasticity orflexibility of the inner wall 1495 is achieved by altering its radius ofcurvature, its thickness, or by changing its convexity/concavityprofile, or through a combination of these. As shown in FIG. 17A, theinner vacuum channel wall 1495 is also optionally configured to bias thegasket valve control region 1481 against the port wall or seat 196 ofthe cassette valve, so that an effective seal is formed under positivepressure, and at least a limited seal is formed under ambient pressure.This allows a valve seal to be maintained even if there is a smallpositive pressure difference between the cassette valve well 183 and theport 173A of the pressure delivery block behind the gasket 148. Thisconfiguration of the gasket valve control region satisfies conflictingconstraints imposed on the functioning of the cassette valve: to ensurecontinuous patency of the vacuum channel 1491, to ensure an adequatecassette valve opening area 402 under negative pressure, and to preserveadequate closure of the cassette valve under positive pressure (andoptionally limited closure properties under ambient pressureconditions).

Variations in Valve Control Regions of the Control Gasket

In some cases, liquid flow through an open valve of the cassette may beimpeded if the valve control surface does not pull the adjacent cassettemembrane sufficiently far away from the valve seat (which in anembodiment, comprises a raised circumferential wall around the valveport or orifice). This is more likely to be an issue when a pump chamberis in a filling mode, applying negative pressure to one or more liquidflowpaths that include one of the cassette valves. In this circumstance,negative pressure transmitted to the liquid passing through the valveorifice may oppose the negative pneumatic pressure applied by the valvecontrol surface of the gasket to keep the cassette membrane an adequatedistance from the valve seat 184. The flow rate of liquid passingthrough the valve may be adversely affected, and opposing forces pullingat the membrane-gasket unit could lead to undesirable vibrations of thecassette membrane and/or gasket valve control region, generating noiseduring liquid flow through the valve orifice. For example, a high liquidflow rate through the valve may further reduce the pressure at the valvethrough a venturi effect, providing additional force opposing theopening force being applied through the valve control region of thecontrol gasket. This could in theory set up an oscillation of the valvemembrane due to variations in the opposing forces, leading toundesirable vibratory noise and an overall reduced flow rate of liquidthrough the valve.

Therefore in some cases, it may be desirable to alter certain propertiesof the gasket valve control region to limit this effect. Some of thevariables suitable for alteration may include the shape, convexity,elasticity, and thickness of the gasket at the valve control region.Similar changes can be considered for the cassette membrane adjacent thecassette valves, but may be more difficult to implement due to otherconstraints placed on the cassette membrane (such as, for example, therequirements for the membrane to operate properly, predictably andreliably in the region of the pump chambers). There may also beconstraints on the choice of composition of the cassette membrane due tothe fact that it must contact and propel fluids that are infused into apatient. The cassette membrane may not therefore have the sameelasticity as that of the adjacent gasket control region.

In an example, a system controller can be programmed to limit thefilling pressure delivered to a pump chamber, so that any negativepressure transmitted to a valve orifice on the cassette connected to thepump chamber is lower than the negative pressure delivered to theadjacent gasket valve control region. The difference in negativepressures at the valve control region must be sufficient to ensure thatthe valve orifice is open to fluid flow. For example, if the negativepressure source for the system is approximately −40 kPa, this pressurecan be delivered to the valve control region of the control gasket, andit or a lower negative pressure also can be delivered to the potentialspace between the control gasket and cassette membrane to encouragein-tandem motion of the gasket valve control region and its adjacentcassette membrane. However, the negative pressure delivered to aconnected pump control region can be regulated to a lower negativepressure, such as, for example, −25 kPa, so that the associated negativepressure transmitted to the liquid flowing through the valve cannotovercome the valve-opening pressure of the gasket valve control region.However, if the gasket valve control region does not pull the cassettemembrane sufficiently far enough from the valve orifice, then aresulting high liquid flow through the valve orifice could furtherreduce the pressure at the valve orifice, causing the cassette membraneand/or valve control region of the gasket to vibrate toward and awayfrom the valve orifice as liquid flow and pressure begins to vary. Insome circumstances, this could reduce the overall liquid flow ratethrough the valve, and potentially create undesirable vibration noise.

Alternate configurations of the gasket valve control region mayameliorate this problem. But any change in the gasket valve controlregion should be balanced against the ability of the system to reliablyseal the cassette membrane against the cassette valve seat when positivepressure is delivered to the valve control region of the gasket.

FIGS. 15A-C show how a valve control region 1481 of a previous ortypical gasket or control surface 148 has been arranged. The elastomericor elastic valve control region 1481 is biased in a valve closing (orvalve seat occluding) position, with an external dome-shaped surfaceextending above the overall plane 1479 of the gasket 148 (i.e. the planeformed by the non-valve or pump control regions of the control gasket148). At least some of the applied negative pressure at port 173A mustbe expended to overcome this bias to invert the valve control region1481, resulting in less force being available to pull the adjacentcassette membrane away from the valve seat 196. FIGS. 18A-23C showexamples of valve control regions 1481A-F of the control gasket 148 inwhich the shape or configuration of the gasket valve control region hasbeen altered to affect the dynamics of opening and closing the valveunder any given positive or negative pneumatic pressure. The valvecontrol regions are shown in resting or unstressed positions. In thesecases, the valve control regions 1481 do not rise above the plane 1479of the gasket 148 (i.e. the plane formed by non-control regions of thegasket). This is in contrast to the valve control region shown in FIGS.15A-C. Any inherent elastic bias in the valve control regions will beless likely to apply a closing pressure against the adjacent cassettemembrane and thus the valve seat. Less force will be needed to pull thegasket/membrane combination away from the valve seat, allowing forincreased space between the cassette membrane and the valve seat andthus increased flow of liquid through the valve. At least a portion ofthe valve control region at rest does not apply pressure to the cassettemembrane and thus does not apply pressure against the valve seat.

In the valve control region configurations shown in FIGS. 18A-18C and20A-20C, the inverted shape of the control regions 1481A, 1481C allowsall of the applied negative pressure to be directed to pulling thegasket/cassette membrane combination away from the valve seat 196.However, less closing pressure for the cassette membrane against thevalve seat 196 will be available for any given application of positivepneumatic pressure through port 173A.

The valve control region 1481B configuration shown in FIGS. 19A-C isbiased toward the cassette membrane and valve seat 196, which must beovercome before the cassette membrane can be pulled away from the valveseat 196. However, the depth of the vacuum channel 1491A at the junctionbetween the valve control region 1481B and the main gasket 148 isincreased (forming essentially a circumferential pleat around the valvecontrol region), increasing the flexibility of the region to move, whichallows the valve control region 1481B to be inverted with less appliednegative pressure. This in turn allows a greater degree of valve openingfor any given negative pressure applied via port 173A.

A similar but inverted radius of curvature is incorporated in theinverted valve control region 1481A of FIGS. 18A-18C. This in turnallows more of an applied positive force through port 173A to beexpended in pressing the cassette membrane against the valve seat 196when the valve needs to be closed. But in this case, the vacuum channelmay be compromised unless accommodations are made for it in molding thegasket 148.

The valve control region 1481C of the arrangement shown in FIGS. 20A-Cprovides an inverted shape, which facilitates the lifting of thecassette membrane from the valve seat 196 under negative pressure. Thereis a reduced transition region between the actuation region 1481C andthe surrounding gasket 148, which could result in less positive forcebeing available to seal the cassette membrane against the valve seat196. The presence or patency of a vacuum channel may be compromised inthis configuration, but this configuration may also allow for less airvolume being trapped between the gasket 148 and cassette membrane 15when air is evacuated between the two surfaces. The valve control region1481D of FIGS. 21A-C provides a similar effect, and likely provides formaximal elimination of any air pockets between cassette membrane andgasket. Although the vacuum channel may be compromised, in these casesthe movement of the valve control region 1481D of the gasket 148 islikely to be more faithfully reproduced by the adjacent cassettemembrane 15 (there being less dampening effect caused by the present ofone or more air pockets in the intervening space).

The arrangement shown in FIGS. 22A-C provides a control gasket valvecontrol region 1481E that is partially folded or pleated, creating arippling or undulation of the surface. The material forming the valvecontrol region has been molded to have a rippled, wavy, or undulatedform, preferably arranged in a concentric manner across the valvecontrol region 1481E. This results in a surface area of material formingthe valve control region 1481E being greater than a surface areaprovided to the valve control region on the plane 1479 of the controlgasket. In this case, the rippled surface of the valve control region1481E of the control gasket 148 adds an amount of slack or floppinessthat provides for enhanced transmission of opening or closing forcesagainst the valve seat 196 (with less expenditure of pressure to deformthe valve control region away from its biased configuration at rest).The effect in this case is to increase the slack or floppiness of thevalve control region 1481E, which facilitates its movement both towardand away from the valve seat 196. In the example shown, the controlregion 1481E forms a crest 1494 opposite the valve orifice 184, andforms a trough opposite the valve seat edge 196 (see, e.g., FIG. 22B).The operation of this valve control region 1481E may be expected toallow for reliable closing of the valve for any given application ofpositive pressure, but the opening created around the valve seat may notbe fully optimized.

It is also more likely that in this arrangement, air pockets or gapsbetween the cassette membrane and valve control region 1481E of thegasket 148 may not be fully evacuated, because of the difference betweenthe surface area of the material forming the cassette membrane 15 valvecontrol region and the surface area of the material forming the valvecontrol region 1481E of the gasket. The degree of rippling of the valvecontrol region 1481E can be controlled in the molding process so thatthe cassette membrane 15 continues to move in tandem with the gasketvalve control region 1481E in a manner sufficient to preserve adequateoperation of the valve.

In contrast, the valve control region 1481F of the control gasket 148depicted in FIGS. 23A-C may provide a more appropriate balance betweenmaximizing the opening of the valve under negative pressure andproviding a reliable and leak-free closure of the valve when positivepressure is applied. The material forming the valve control region 1481Fhas been molded to have a rippled, wavy or undulating form, in this caseforming concentric ripples across the valve control region 1481F. Thisresults in a surface area of material forming the valve control regionbeing greater than a surface area provided by the valve control regionon the plane 1479 of the control gasket. In this case, the rippledsurface of the valve control region 1481F of the control gasket 148 addsan amount of slack or floppiness that provides for enhanced transmissionof opening or closing forces against the valve seat 196 (with lessexpenditure of pressure to deform the valve control region away from itsbiased configuration at rest). In the example shown, the crest 1496 ofthe ripple pattern is opposite the edge or wall 196 of the valve seat,with the trough 1498 now being located at the center of the valvecontrol region, opposite the valve orifice 184, as shown in FIG. 23B.This creates a bias in the gasket oriented toward sealing the cassettemembrane 15 against the valve seat 196, while still providing forrelatively unrestricted movement of the valve control region 1481F underboth positive and negative pressure. This arrangement may provide animproved compromise between both opening and closing the valve. Reliableand effective valve closure is achieved under positive pressure, whileenhanced fluid flow across the valve and reduced membrane oscillationand vibratory noise are achieved under negative pressure. In thisembodiment, a secondary trough outside the valve seat 196 may functionas a vacuum channel 1491B.

FIG. 24 shows an exploded view of an integrated pressure distributionmodule or assembly 2700 for use in a fluid flow control apparatus foroperating a pumping cassette, and suitable for use as pressuredistribution manifold 172 and mating block 170 of cycler 14. FIG. 25shows an assembled view of integrated module 2700. The integrated module2700 shown in these drawings comprises a pneumatic manifold or block172, ports 2714 for supply pressures, pneumatic control valves 2710,pressure sensors 2740, a pressure delivery or mating block 170 and acontrol surface or actuator 148 that includes regions comprisingflexible membranes for actuating pumps 171B and valves 171A on a pumpingcassette. The integrated module 2700 may also include reference chambers174 within the pneumatic manifold 172 for a pressure/volume measurementprocess for determining the volume of fluid present in a pumping chamberof a pumping cassette based on the ideal gas laws. The integrated module2700 may also comprise a vacuum port 1483 (in the gasket 148—see e.g.FIG. 11), a mating vacuum port 173B of the pressure delivery block 170(see, e.g. FIG. 13 or FIG. 14) and a set of pathways or channels frominterfaces between the actuator or gasket 148 and flexible pump andvalve membranes 15 of a pumping cassette to a fluid trap 1722 and liquiddetection system 2670 in the manifold 172 (see, e.g., the pressuredistribution schematic illustrated in FIG. 26). In some embodiments, thepneumatic manifold 172 may be formed as a single block. In otherembodiments, the pneumatic manifold 172 may be formed from two or moremanifold blocks mated together with gaskets positioned between themanifold blocks. The integrated module 2700 occupies a relatively smallspace in a fluid flow control apparatus, and eliminates the use of tubesor flexible conduits connecting the manifold ports with correspondingports of a pressure delivery module or block mated to a pumpingcassette. Among other possible advantages, the integrated module 2700reduces the size and assembly cost of the pneumatic actuation assemblyof a peritoneal dialysis cycler, which may result in a smaller and lessexpensive cycler. Additionally, the short distances between pressure orvacuum distribution ports on the pressure distribution manifold blockand corresponding pressure or vacuum delivery ports 173A, 173B, 173C ona mating pressure delivery block 170, together with the rigidity of theconduits connecting the ports, may improve the responsiveness of anattached pumping cassette and the accuracy of cassette pump volumemeasurement processes. When used in a peritoneal dialysis cycler 14, inan embodiment, an integrated module comprising a metallic pressuredistribution manifold mated directly to a metallic pressure deliveryblock may also reduce any temperature differences between the controlvolume 171B and the reference chamber 174 of the cycler 14, which mayimprove the accuracy of the pump volume measurement process.

An exploded view of the integrated module 2700 is presented in FIG. 24.The actuator surface, mounted on a mating block or pressure deliveryblock, is analogous or equivalent to the gasket or control surface 148,that includes flexible regions arranged to move back and forth to pumpfluid and/or open and close valves by pushing or pulling on a membrane15 of a pump cassette 24. With respect to cycler 14, the control gasket148 is actuated by the positive and negative pneumatic pressure suppliedto the control volumes 171A, 171B behind the control regions 1481, 1482.The control gasket 148 attaches to the pressure delivery block or matingblock 170 by fitting tightly on a raised surface 2744 on the frontsurface of the mating block 170 with a lip 2742. The mating block 170may include one or more surface depressions 2746 to align with andsupport the oval curved shape of one or more corresponding pump controlsurfaces 1482, forming a pump control chamber. A similar arrangement,with or without a surface depression, may be included in forming a valvecontrol region 171A to align with a corresponding control surface 1481for controlling one or more valves of a pumping cassette. The matingblock 170 may further include grooves 2748 on the surface of depression2746 of mating block 170 behind the pump control surface 1482 tofacilitate the flow of control fluid or gas from the port 173C to theentire back surface the pump control surface 1482. Alternatively, ratherthan having grooves 2748, the depression 2746 may be formed with aroughened surface or a tangentially porous surface.

The mating block 170 connects the pressure distribution manifold 172 tothe control gasket 148, and delivers pressure or vacuum to variouscontrol regions on control gasket 148. The mating block 170 may also bereferred to as a pressure delivery block in that it provides pneumaticconduits to supply pressure and vacuum to the valve control regions 1481and the pump control regions 1482, vacuum to the vacuum ports 1483 andconnections from the pump control volumes 171B to the pressure sensors.The ports 173A connect the valve control volumes 171A to the pressuredistribution manifold 172. The ports 173C connect the pump controlvolume 171B to the pressure distribution manifold 172. The vacuum ports1483 are connected to the pressure distribution manifold 172 via ports173B. In one embodiment, the ports 173B extend above the surface of thepressure delivery block 170 to pass through the control gasket 148 toprovide vacuum at port 1483 without pulling the control surface 148 ontothe port 173B and blocking flow.

The pressure delivery block 170 is attached to the front face of thepressure distribution manifold 172. The ports 173A, 173B, 173C line upwith pneumatic circuits on the pressure distribution manifold 172 thatconnect to valve ports 2714. In one example, the pressure delivery block170 is mated to the pressure distribution manifold 172 with a front flatgasket 2703 clamped between them. The block 170 and manifold 172 areheld together mechanically, which in an embodiment is through the use ofbolts 2736 or other types of fasteners. In another example, rather thana flat gasket 2703, compliant elements are placed in or molded in eitherthe pressure delivery block 170 or the pressure distribution manifold172. Alternatively, the pressure delivery block 170 may be bonded to thepressure distribution manifold 172 by an adhesive, double sided tape,friction welding, laser welding, or other bonding method. The block 170and manifold 172 may be formed of metal or plastic and the bondingmethods will vary depending on the material.

The pressure distribution manifold 172 contains ports for the pneumaticvalves 2710, reference chambers 174, a fluid trap 1722 and pneumaticcircuitry or of the integrated module 2700 connections providespneumatic connections between the pressure reservoirs, valves, andcontains ports 2714 that receive multiple cartridge valves 2710. Thecartridge valves 2710 include but are not limited to the binary valves2660 controlling flow to valve control volumes 171A, the binary valvesX1A, X1B, X2, X3 controlling flow to pump control volumes 171B, and thebinary valves 2661-2667 controlling flow to the bladders 2630, 2640,2650 and pressure reservoirs 2610, 2620. The cartridge valves 2710 arepressed into the valve ports 2714 and electrically connected to thehardware interface 310 via circuit board 2712.

The pneumatic circuitry in the pressure distribution manifold 172 may beformed with a combination of grooves or slots 1721 on the front and backfaces and approximately perpendicular holes that connect the grooves1721 on one face to valve ports 2714, the fluid trap 1722 and to groovesand ports on the opposite face. Some grooves 1721 may connect directlyto the reference chambers 174. A single perpendicular hole may connect agroove 1721 to multiple valve ports 174 that are closely spaced andstaggered. Sealed pneumatic conduits are formed when the grooves 1721are isolated from one another by, in one example, the front flat gasket2703 as shown in FIG. 24.

The presence of liquid in the fluid trap 1722 (FIG. 26) may be detectedby a pair of conductivity probes 2732 (FIG. 24). The conductivity probes2732 slide through a back gasket 2704, a back plate 2730 and holes 2750before entering the fluid trap 1722 in the pressure distributionmanifold 172.

The back plate 2730 seals the reference volumes 174, the grooves 1721 onthe back face of the pressure distribution manifold 172 and providesports for the pressure sensors 2740 and ports for pressure and vacuumlines 2734 and vents to the atmosphere 2732. In one example, thepressure sensors may be IC chips soldered to a single board 2740 andpressed as a group against the back gasket 2704 on the back plate 2730.In one example, bolts 2736 clamp the back plate 2730, pressuredistribution manifold 172 and pressure delivery block 170 together withgaskets 2703, 2702 between them. In another example, the back plate 2730may be bonded to the pressure delivery manifold 172 as described above.The assembled integrated module 2700 is presented in FIG. 26.

FIG. 26 presents a schematic of the pneumatic pressure circuit in theintegrated manifold 2700 and pneumatic elements outside the manifold.The pump 2600 produces vacuum and pressure. The pump 2600 is connectedvia 3 way valves 2664 and 2665 to a vent 2680 and the negative or vacuumreservoir 2610 and the positive reservoir 2620. Pressures in thepositive and negative reservoirs 2620, 2610 are measured respectively bypressure sensors 2678, 2676. The hardware interface 310 controls thespeed of the pump 2600 and the position of 3-way valves 2664, 2665, 2666to control the pressure in each reservoir. The auto-connect stripperelement bladder 2630 is connected via 3-way valve 2661 to either thepositive pressure line 2622 or the negative or vacuum line 2612. Theautomation computer 300 commands the position of valve 2661 to controlthe location of the stripper element 1461. The occluder bladder 2640 andpiston bladder 2650 are connected via 3-way valves 2662 and 2663 toeither the pressure line 2622 or vent 2680. The automation computer 300commands valve 2663 to connect the piston bladder 2650 to the pressureline 2622 after the door 141 is closed to securely engage the cassette24 against the control gasket 148. The occluder bladder 2640 isconnected to the pressure line 2622 via valve 2662 and restriction 2682.The occluder bladder 2640 is connected to the vent 2680 via valve 2662.The orifice 2682 advantageously slows the filling of the occluderbladder 2640 that retracts the occluder 147 in order to maintain thepressure in the pressure line 2622. The high pressure in the pressureline 2622 keeps the various valve control surfaces 171A and the pistonbladder 2650 actuated against the cassette 24, which prevents flow to orfrom the patient as the occluder 147 opens. Conversely the connectionfrom the occluder bladder 2640 to the vent 2680 is unrestricted, so thatoccluder 147 can quickly close.

The valve control surfaces 1481 are controlled by the pressure in thevalve control volume 171A, which in turn is controlled by the positionof the 3-way valves 2660. The valves 2660 can be controlled individuallyvia commands from the automation computer 300 passed to the hardwareinterface 310. The valves controlling the pumping pressures in the pumpcontrol volumes 171B are controlled with 2-way valves X1A, X1B. Thevalves X1A, X1B in one example may be controlled by the hardwareinterface 310 to achieve a pressure commanded by the automation computer300. The pressure in each pump control chamber 171B is measured bysensors 2672. The pressure in the reference chambers is measured bysensors 2670. The 2-way valves X2, X3 respectively connect the referencechamber 174 to the pump control chamber 171B and the vent 2680.

The fluid trap 1722 is connected to the vacuum line 2612 duringoperation as explained elsewhere in this application. The fluid trap1722 is connected by several lines to the ports 173B in the pressuredelivery block 170. The pressure in the fluid trap 1722 is monitored bypressure sensor 2674 that is mounted on the back plate 2730.

The vacuum ports 1483 may be employed to separate the membrane 15 fromthe control gasket 148 at the end of therapy before or during theopening the door. The vacuum provided by the negative pressure source tothe vacuum ports 1483 sealingly engages the membrane 15 to the controlgasket 148 during therapy. In some instances a substantial amount offorce may be needed to separate the control surface from the cassettemembrane 15, preventing the door 141 from freely rotating into the openposition, even when the application of vacuum is discontinued. Thus, inan embodiment, the pressure distribution module 2700 is configured toprovide a valved channel between the positive pressure source and thevacuum ports 1483. Supplying positive pressure at the vacuum ports 1483may aid in separating the membrane 15 from the control gasket 148,thereby allowing the cassette 24 to separate more easily from thecontrol gasket 148 and allow the door 141 to open freely. The pneumaticvalves in the cycler may be controlled by the automation computer 300 toprovide a positive pressure to the vacuum ports 1483. The manifold 172may include a separately valved channel dedicated for this purpose, oralternatively it may employ the existing channel configurations andvalves, operated in a particular sequence.

In one example, the vacuum ports 1483 may be supplied with positivepressure by temporarily connecting the vacuum ports 1483 to the positivepressure reservoir 2620. The vacuum ports 1483 are normally connected tothe vacuum reservoir 2610 via a common fluid collection chamber or fluidtrap 1722 in the manifold 172 during therapy. In one example, thecontroller or automation computer may open valve X1B between thepositive pressure reservoir and the volume control chamber 171B and thevalve X1A between the negative pressure reservoir and the same volumecontrol chamber 171B simultaneously, which will pressurize the air inthe fluid trap 1722 and the vacuum ports 1483. The pressurized air willflow through the vacuum ports 1483 and between the membrane 15 and thecontrol gasket 148, breaking any vacuum bond between the membrane andcontrol surface. However, in the illustrated manifold, the stripperelement 1491 of the cap stripper 149 may extend while the positivepressure is supplied to common fluid collection chamber 1722 fluid,because the stripper bladder 2630 is connected to a the vacuum supplyline 2612. In this example, in a subsequent step, the fluid trap 1722may be valved off from the now-pressurized vacuum line and the twovalves X1A, X1B connecting the positive and vacuum reservoirs to thevolume control chamber 171B may be closed. The vacuum pump 2600 is thenoperated to reduce the pressure in the vacuum reservoir 2610 and thevacuum supply line 2612, which in turn allows the stripper element 1491to be withdrawn. The door 141 may then be opened after detaching thecassette 24 from the control gasket 148 and retracting the stripperelement 1491.

In accordance with an aspect of the disclosure, the vacuum ports 1483may be used to detect leaks in the membrane 15, e.g., a liquid sensor ina conduit or chamber connected to a vacuum port 1483 may detect liquidif the membrane 15 is perforated or liquid otherwise is introducedbetween the membrane 15 and the control gasket 148. For example, vacuumports 1483 may align with and be sealingly associated with complementaryvacuum ports 173B in mating block 170, which in turn may be sealinglyassociated with fluid passages 1721 leading to a common fluid collectionchamber 1722 in manifold 172. The fluid collection chamber 1722 maycontain an inlet through which vacuum can be applied and distributed toall vacuum ports 1483 of control gasket 148. By applying vacuum to thefluid collection chamber 1722, fluid may be drawn from each of thevacuum ports 173B and 1483, thus removing fluid from any space betweenthe membrane 15 and the control gasket 148 at the various controlregions. However, if there is liquid present at one or more of theregions, the associated vacuum port 1483 may draw the liquid into thevacuum ports 173B and into the lines 1721 leading to the fluidcollection chamber 1722. Any such liquid may collect in the fluidcollection chamber 1722, and be detected by one or more suitablesensors, e.g., a pair of conductivity sensors that detect a change inconductivity in the chamber 1722 indicating the presence of liquid. Inthis embodiment, the sensors may be located at a bottom side of thefluid collection chamber 1722, while a vacuum source connects to thechamber 1722 at an upper end of the chamber 1722. Therefore, if liquidis drawn into the fluid collection chamber 1722, the liquid may bedetected before the liquid level reaches the vacuum source. Optionally,a hydrophobic filter, valve or other component may be placed at thevacuum source connection point into the chamber 1722 to help furtherresist the entry of liquid into the vacuum source. In this way, a liquidleak may be detected and acted upon by controller 16 (e.g., generatingan alert, closing liquid inlet valves and ceasing pumping operations)before the vacuum source valve is placed at risk of being contaminatedby the liquid.

In the example schematic shown in FIG. 26, a calibration port 2684 isdepicted. The calibration port 2684 may be used to calibrate the variouspressure sensors 2670, 2672, 2674, 2676, 2677, 2678 in the pneumaticsystem. For example, a pressure reference may be connected to thepneumatic circuit of the cycler via the calibration port 2684. With thepressure reference connected, the valves of the pneumatic system may beactuated so as to connect all of the pressure sensors 2670, 2672, 2674,2676, 2677, 2678 to the same fluid volume. A known pressure may then beestablished in the pneumatic system using the pressure reference. Thepressure readings from each of the pressure sensors 2670, 2672, 2674,2676, 2677, 2678 may be compared to the known pressure of the pressurereference and the pressure sensors 2670, 2672, 2674, 2676, 2677, 2678may then be calibrated accordingly. In some embodiments, selectedpressure sensors of the pressure sensors 2672, 2674, 2676, 2677, 2678may be connected and brought to the pressure of the reference forcalibration in groups or individually.

Any fluid handling device (i.e. base unit) that is configured to actuatediaphragm-based pumps and valves on a removable cassette can takeadvantage of its pneumatic (or hydraulic) cassette interface to receivea calibrating reference pressure via a specialized calibrating cassette(or ‘cassette fixture’). A calibrating cassette can have the sameoverall dimensions as a standard fluid pumping cassette, so that it canprovide a sealing interface with the cassette interface or controlsurface of the base unit. One or more of the pump or valve regions canbe allowed to communicate with a corresponding region of the interfaceto which it mates, so that a reference pneumatic or hydraulic pressurecan be introduced through the calibrating cassette and into thepneumatic or hydraulic flow paths of the base unit (e.g. via a pneumaticor hydraulic manifold).

For example, in a pneumatically operated peritoneal dialysis cycler, thepneumatic circuitry of the cycler may be accessed directly through thecassette interface of the cycler. This may for example, be accomplishedusing a modified cassette or cassette fixture which allows the controlsurface 148 to create a seal against the cassette fixture. Additionally,the cassette fixture may be constructed to include at least one accessport in fluid communication with a vacuum port 173B of the cassetteinterface. In the absence of a vacuum port (e.g. in embodiments havingslits or perforations in the control surface) the access port mayinstead be placed in communication with the vacuum vent feature of thecassette interface or control surface.

The cassette fixture (or calibrating cassette) may be constructed tohave a direct flow path from an external cassette port to the accessport facing the device interface, the external cassette port then beingavailable for connection to a pressure reference. As described above,all or some of the pressure sensors 2670, 2672, 2674, 2676, 2677, 2678may be placed into fluid communication with a common volume, through theappropriate actuation of pneumatic control valves in the pressuredistribution manifold. A known pressure may be established in thatvolume using the pressure reference. The pressure readings from each ofthe pressure sensors 2670, 2672, 2674, 2676, 2677, 2678 may be comparedto the known pressure of the pressure reference and the pressure sensors2670, 2672, 2674, 2676, 2677, 2678 may then be calibrated accordingly.

In some embodiments of a pressure distribution manifold, it may not bepossible for all of the pressure sensors 2670, 2672, 2674, 2676, 2677,2678 to be connected to a common volume at one time. In that case, theflow paths to the individual pressure sensors 2670, 2672, 2674, 2676,2677, 2678 may need to be opened in a sequential manner to ensurecalibration of all sensors. Additionally, it should be noted that oncecalibrated, one or more of the pressure sensors 2670, 2672, 2674, 2676,2677, 2678 may be used to calibrate other pressure sensors 2670, 2672,2674, 2676, 2677, 2678 in a pressure distribution manifold of a baseunit or cycler. The previously calibrated pressure sensor or sensors maybe placed into a common volume with the uncalibrated pressure sensor(e.g. via suitable valve actuations). The pressure of the common volumemay be known via the calibrated pressure sensor(s). The uncalibratedpressure sensor's reading may be compared to the known pressure of thecommon volume and then calibrated accordingly.

FIG. 27 depicts a schematized view of an embodiment of a cassettefixture 4570. As shown, the cassette fixture 4570 has the same outlineas a standard pump cassette 24 described earlier. The cassette fixture4570 includes an access port 4572 associated with a specific valve orpump region of a standard cassette to align with its correspondingregion on the cassette interface (control surface 148) of the base unit.The cassette fixture 4570 otherwise can have a flat smooth interfacesurface to allow the control surface to seal against it when it is matedto the base unit or cycler. Preferably, the cassette fixture 4570 isformed from a metal or other hard, stiff material. A resistance toflexing or deformation under pressure may help to increase reliabilityand consistency over multiple calibrations of multiple cyclers. Asshown, the cassette fixture 4570 includes an access port 4572 which isrecessed into the face of the cassette fixture 4570. The access port4572 communicates with a fluid path 4573 extending to tubing 4574leading away from the cassette fixture 4570. A cassette port or fittingmay be included on the side of the cassette for connection via tubing toa reference pressure source 4576 in the example embodiment.

FIGS. 28 and 29 depict other representations of a cassette fixture 4570adapted from a modified cassette such as the cassette 24 shown in FIG.3. In such examples, the cassette fixture 4570 may be made by removingor not including the sheeting or membrane 15 from the control side ofthe cassette which faces a control surface or cassette interface 148(see, for example, FIG. 90) of a cycler when installed in the cycler.Referring to FIG. 3, for example, the membrane 15 may not be included onthe cassette 24. Thus, the pneumatic circuit of the cycler may beaccessed directly through the cassette 24. Alternatively, the membraneor sheeting may be interrupted (e.g. removed, perforated, slit, or thelike) on only a portion of the cassette to create the cassette fixture4570. For example, the membrane may be modified in this manner in thearea over which an access port 4572 of the cassette fixture 4570 islocated.

Additionally, tubing 4574 may be attached to one or more of the externalconnection sites of a standard cassette to create the necessary fluidcommunication path of a cassette fixture 4570. The external connectionsites can include any tubing attachment sites on the standard cassette,or may comprise more robust fittings for repeated use in calibrationprocedures. Referring to FIG. 3, external connection sites may includethe cassette spikes 160 and/or the ports 150, 152 and 154. The cassettemay then be modified so that all other external connection sites may beblocked, plugged or otherwise sealed.

As above, the tubing 4574 leads from a fluid flowpath 4573 fluidicallyconnected to an access port 4572 in the cassette fixture 4570 to providea connection path to a pressure reference 4576. The access port 4572 maybe a pre-existing opening or valve port in the cassette body.Additionally, the fluid path 4573 may be any pre-existing pathway orcombination of pathways in the cassette body which allow fluidcommunication from the access port 4572 to the tubing 4574 or anassociated fitting on the side of the cassette. For example, a fluidpath 4573 may include one or more valve port, valve well, pump chamber,and/or channel in the cassette body or any combination thereof.

In one embodiment, the inner wall of the control chambers 171B caninclude raised elements somewhat analogous to the spacer elements 50 ofthe pump chamber, e.g., as shown in FIG. 13 for the control chambers171B associated with the pump control regions 1482. These raisedelements can take the form of plateau features, ribs, or otherprotrusions that keep the control ports recessed away from the fullyretracted control regions 1482. This arrangement may allow for a moreuniform distribution of pressure or vacuum in the control chamber 171B,and prevent premature blocking of any control port by the control gasket148. A pre-formed control gasket 148 (at least in the pump controlregions) may not be under a significant stretching force when fullyextended against either the inner wall of the pump chamber of thecassette 24 during a delivery stroke, or the inner wall of the controlchamber 171 during a fill stroke. It may therefore be possible for thecontrol region 1482 to extend asymmetrically into the control chamber171B, causing the control region 1482 to prematurely close off one ormore ports of the control chamber before the chamber is fully evacuated.Having features on the inner surface of the control chamber 171B thatprevent contact between the control region 1482 and the control portsmay help to assure that the control region 1482 can make uniform contactwith the control chamber inner wall during a fill stroke.

As suggested above, the cycler 14 may include a control system 16 with adata processor in electrical communication with the various valves,pressure sensors, motors, etc., of the system and is preferablyconfigured to control such components according to a desired operatingsequence or protocol. The control system 16 may include appropriatecircuitry, programming, computer memory, electrical connections, and/orother components to perform a specified task. The system may includepumps, tanks, manifolds, valves or other components to generate desiredair or other fluid pressure (whether positive pressure—above atmosphericpressure or some other reference—or negative pressure or vacuum—belowatmospheric pressure or some other reference) to control operation ofthe regions of the control gasket 148, and other pneumatically-operatedcomponents. Further details regarding the control system 16 (or at leastportions of it) are provided below.

In one illustrative embodiment, the pressure in the pump controlchambers 171B may be controlled by a binary valve, e.g., which opens toexpose the control chamber 171 to a suitable pressure/vacuum and closesto cut off the pressure/vacuum source. The binary valve may becontrolled using a saw tooth-shaped control signal which may bemodulated to control pressure in the pump control chamber 171B. Forexample, during a pump delivery stroke (i.e., in which positive pressureis introduced into the pump control chamber 171B to move the membrane15/control gasket 148 and force liquid out of the pump chamber 181), thebinary valve may be driven by the saw tooth signal so as to open andclose at a relatively rapid rate to establish a suitable pressure in thecontrol chamber 171B (e.g., a pressure between about 70-90 mmHg). If thepressure in the control chamber 171B rises above about 90 mmHg, the sawtooth signal may be adjusted to close the binary valve for a moreextended period. If the pressure drops below about 70 mmHg in thecontrol chamber 171B, the saw tooth control signal may again be appliedto the binary valve to raise the pressure in the control chamber 171.Thus, during a typical pump operation, the binary valve will be openedand closed multiple times, and may be closed for one or more extendedperiods, so that the pressure at which the liquid is forced from thepump chamber 181 is maintained at a desired level or range (e.g., about70-90 mmHg).

In some embodiments, it may be useful to detect an “end of stroke” ofthe membrane 15/pump control region 1482, e.g., when the membrane 15contacts the spacers 50 in the pump chamber 181 or the pump controlregion 1482 contacts the wall of the pump control chamber 171B. Forexample, during a pumping operation, detection of the “end of stroke”may indicate that the membrane 15/pump control region 1482 movementshould be reversed to initiate a new pump cycle (to fill the pumpchamber 181 or drive fluid from the pump chamber 181). In oneillustrative embodiment in which the pressure in the control chamber171B for a pump is controlled by a binary valve driven by a saw toothcontrol signal, the pressure in the pump chamber 181 will fluctuate at arelatively high frequency, e.g., a frequency at or near the frequency atwhich the binary valve is opened and closed. A pressure sensor in thecontrol chamber 171B may detect this fluctuation, which generally has ahigher amplitude when the membrane 15/pump control region 1482 are notin contact with the inner wall of the pump chamber 181 or the wall ofthe pump control chamber 171B. However, once the membrane 15/pumpcontrol region 1482 contacts the inner wall of the pump chamber 181 orthe wall of the pump control chamber 171B (i.e., the “end of stroke”),the pressure fluctuation is generally damped or otherwise changes in away that is detectable by the pressure sensor in the pump controlchamber 171B. This change in pressure fluctuation can be used toidentify the end of stroke, and the pump and other components of thecassette 24 and/or cycler 14 may be controlled accordingly.

In one embodiment, the pneumatic pressure applied to the control chamber171B is actively controlled by a processor receiving a signal from apressure transducer 2672 (FIG. 26) connected to the control chamber 171Band a fast acting binary valve X1A, X1B between a pressure reservoir2620, 2610 and the control chamber 171B. The processor may control thepressure with a variety of control algorithms including closed loopproportional or proportional-integrator feedback control that varies thevalve duty cycle to achieve the desired pressure in the control volume171B. In one embodiment, the processor controls the pressure in thecontrol chamber with an on-off controller often called a bang-bangcontroller. The on-off controller monitors the pressure in the controlvolume 171B during a deliver stroke and open the binary valve X1B(connecting the control volume 171B to the positive reservoir 2620) whenthe pressure is less than a lower first limit and closes the binaryvalve X1B when the pressure is above a higher second limit. During afill stroke, the on-off controller opens the binary valve X1A(connecting the control volume 171B to the negative reservoir 2610) whenthe pressure is greater than a third limit and closes the binary valveX1A when the pressure is less than a fourth limit, where the fourthlimit is lower than the third limit and both the third and fourth limitsare less than the first limit. A plot of the pump control chamberpressure over time during a deliver stroke and the associated pressuremeasurement is shown in FIG. 31. The control chamber pressure oscillatesbetween a lower first limit and a higher second limit as the membrane 15moves across the control chamber 171B. The pressure stops oscillatingbetween the limits when the membrane 15 stops moving. The membrane 15typically stops moving when it contacts either the spacers 50 of thecassette or it contacts the control chamber surface 171B. The membrane15 may also stop moving if the outlet fluid line is occluded.

The automation computer (AC) 300 detects the end of stroke by evaluatingthe pressure signals. There are many possible algorithms to detect theend of pressure oscillation that indicate the end-of-stroke (EOS). Thealgorithms and methods to detect EOS in the section labeled “DetailedDescription of the system and Method of Measuring Change Fluid FlowRate” in U.S. Pat. No. 6,520,747 and the section describing thefiltering to detect end of stroke in U.S. Pat. No. 8,292,594 are hereinincorporated by reference.

One example of an algorithm to detect EOS, the AC 300 evaluates the timebetween the pressure crossing the first and second limits during adeliver stroke or third and fourth limits during a fill stroke. Theon-off controller opens and closes the valves X1A, X1B in response tothe pressure oscillating between the two limits as the control chambervolume changes during the fill or deliver stroke. When the membrane 15stops moving at the end-of-stroke, the pressure changes willsignificantly diminish so that the pressure no longer exceeds one orboth limits. The AC 300 may detect EOS by measuring the time between thepressure exceeding alternating limits. If the time since the pressurecrossed the last limit exceeds a predefined threshold, then the AC 300may declare an EOS. The algorithm may further include an initial periodduring which the AC 300 does not measure the time between limitcrossings.

In another example algorithm, the AC 300 evaluates the derivative of thepressure signal with respect to time. The AC 300 may declare an EOS, ifthe derivative remains below a minimum threshold for a minimum length oftime. In a further example, the minimum threshold is the average of theabsolute value of the average pressure derivative during the stroke. Thealgorithm calculates the slope (derivative with respect to time) of acurve fit to a set of data points, where the data points are taken froma moving window. The absolute value of each slope is then averaged overthe stroke to calculate the absolute value of the average pressurederivative. In another example of an EOS algorithm, the AC 300 may notinclude the pressure data until after an initial delay. The AC 300ignores the initial pressure data to avoid false EOS detections due toirregular pressure traces that occasionally occur during the early partof the stroke. In another example, the AC 300 declares an EOS only afterthe second derivative of the pressure in the later part of the strokehas remained below a threshold for a minimum time and a wait period oftime has past.

The criteria to declare an EOS may be optimized for different pumpingconditions. The optimized EOS detection conditions include the secondpressure derivative threshold, the minimum time to remain below thesecond derivative threshold, the duration of the initial delay and alength of the wait period. These EOS detection criteria may be optimizeddifferently, for example, the fill stroke from the bags 20, 22, thedeliver stroke to the patient, the fill stroke from the patient, and thedeliver stroke to the bags 20, 22. Alternatively each EOS detectioncriteria may be a function of the pumping pressure in the controlchamber 171B.

Noise Reduction Features of the Cycler

In accordance with aspects of the invention, the cycler 14 may includeone or more features to reduce noise generated by the cycler 14 duringoperation and/or when idle. In one aspect of the invention, the cycler14 may include a single pump that generates both pressure and vacuumthat are used to control the various pneumatic systems of the cycler 14.In one embodiment, the pump can simultaneously generate both pressureand vacuum, thereby reducing overall run time, and allowing the pump torun more slowly (and thus more quietly). In another embodiment, the airpump start and/or stop may be ramped, e.g., slowly increases pump speedor power output at starting and/or slowly decreases pump speed or poweroutput at shut down. This arrangement may help reduce “on/off” noiseassociated with start and stop of the air pump so pump noise is lessnoticeable. In another embodiment, the air pump may be operated at alower duty cycle when nearing a target output pressure or volume flowrate so that the air pump can continue operating as opposed to shuttingoff, only to be turned on after a short time. As a result, disruptioncaused by repeated on and off cycles of the air pump may be avoided.

FIG. 32 shows a perspective view of an interior section of the cycler 14with the upper portion of the housing 82 removed. In this illustrativeembodiment, the cycler 14 includes a single air pump 83, which includesthe actual pump and motor drive contained within a sound barrierenclosure. The sound barrier enclosure includes an outer shield, such asa metal or plastic frame, and a sound insulation material within theouter shield and at least partially surrounding the motor and pump. Thisair pump 83 may simultaneously provide air pressure and vacuum, e.g., toa pair of accumulator tanks 84. One of the tanks 84 may store positivepressure air, while the other stores vacuum. A suitable manifold andvalve arrangement may be coupled to the tanks 84 so as to provide andcontrol air pressure/vacuum supplied to the components of the cycler 14.

In an embodiment, components that require a relatively constant pressureor vacuum supply during cycler operation, such as an occluder, may beisolated from the source of air pressure/vacuum at least for relativelylong periods of time. For example, the occluder 147 in the cycler 14(shown in FIG. 30) generally requires a constant air pressure in theoccluder bladder 166 so that the patient and drain lines remain open forflow. If the cycler 14 continues to operate properly without powerfailure, etc., the bladder 166 may be inflated once at the beginning ofsystem operation and remain inflated until shut down. The inventors haverecognized that in some circumstances air powered devices that arerelatively static, such as the bladder 166, may “creak” or otherwisemake noise in response to slight variations in supplied air pressure.Such variations may cause the bladder 166 to change size slightly, whichcauses associated mechanical parts to move and potentially make noise.In accordance with an aspect of the bladder 166 and other componentshaving similar pneumatic power requirements, may be isolated from theair pump 83 and/or the tanks 84, e.g., by the closing of a valve, so asto reduce variations of pressure in the bladder or other pneumaticcomponent, thus reducing noise that may be generated as a result ofpressure variations. Another component that may be isolated from thepneumatic supply is the bladder in the door 141 at the cassette mountinglocation 145 which inflates to press the cassette 24 against the controlgasket 148 when the door 141 is closed. Other suitable components may beisolated as desired.

In another embodiment, the speed and/or force at which pneumaticcomponents are actuated may be controlled to as to reduce noisegenerated by component operation. For example, movement of the valvecontrol regions 1481 to move a corresponding portion of the cassettemembrane 15 so as to open or close a valve port on the cassette 24 maycause a “popping” noise as the membrane 15 slaps against and/or pullaway from the cassette 24. Such noise may be reduced by controlling therate of operation of the valve control regions 1481, e.g., byrestricting the flow rate of air used to move the control regions 1481.Air flow may be restricted by, for example, providing a suitably smallsized orifice in the line leading to the associated control chamber, orin other ways.

A controller may also be programmed to apply pulse width modulation(“PWM”) to the activation of one or more pneumatic source valves at amanifold of cycler 14. The effect on a pressure tracing associated witha pump chamber can be seen in FIG. 31. The pneumatic pressure deliveredto various valves and pumps of cassette 24 can be controlled by causingthe associated manifold source valves to open and close repeatedlyduring the period of actuation of a valve or pump in cassette 24. Therate of rise 2300 or fall 2302 of pressure against membrane 15/controlgasket 148 can then be controlled by modulating the duration of the “on”portion of the particular manifold valve during the actuation period. Anadditional advantage of applying PWM to the manifold source valves isthat variable pneumatic pressure can be delivered to the cassette 24components using only a binary (on-off) source valve, rather than a moreexpensive and potentially less reliable variable-orifice source valve.

In another embodiment, the movement of one or more valve elements may besuitably damped so as to reduce noise generated by valve cycling. Forexample, a fluid (such as a ferro fluid) may be provided with the valveelement of high frequency solenoid valves to damp the movement of theelement and/or reduce noise generated by movement of the valve elementbetween open and closed positions.

In another embodiment, pneumatic control line vents may be connectedtogether and/or routed into a common, sound-insulated space so thatnoise associated with air pressure or vacuum release may be reduced. Forexample, when the occluder bladder 166 is vented to allow the springplates 165 (see, for example, FIG. 30) to move toward each other andocclude one or more lines, the air pressure released may be releasedinto a sound insulated enclosure, as opposed to being released into aspace where noise associated with the release may be heard more easily.In another embodiment, lines that are arranged to release air pressuremay be connected together with lines that are arranged to release an airvacuum. With this connection (which may include a vent to atmosphere, anaccumulator or other), noise generated by pressure/vacuum release may befurther reduced.

The invention claimed is:
 1. A method of opening or closing a pumpcassette membrane valve comprising a flexible membrane overlying a valveseat of the pump cassette and using an elastomeric valve control regionof a gasket placed between the flexible membrane of the pump cassetteand a pressure delivery block, the method comprising: pulling theflexible membrane toward the gasket by applying a first negativepressure from the pressure delivery block through a vacuum port in thegasket to an outer side of the gasket valve control region facing thecassette membrane via a vacuum channel located along a periphery of thevalve control region and open to the outer side of the gasket valvecontrol region; applying a second negative pressure from the pressuredelivery block to an inner side of the gasket valve control regionfacing the pressure delivery block to open the membrane valve; flexingan inner wall of the vacuum channel toward the pressure delivery blockand away from pump cassette valve seat to increase a distance betweenthe flexible membrane and the valve seat, the inner wall beingcontiguous with the valve control region of the gasket; and limiting aflexion of an outer wall of the vacuum channel to maintain patency ofthe vacuum channel during the opening of the membrane valve so that thefirst negative pressure applied to the outer side of the gasket valvecontrol region is uninterrupted.
 2. The method of claim 1, whereinapplying the first and second negative pressure comprises applyingnegative pneumatic pressure.
 3. The method of claim 1, wherein applyingthe first negative pressure comprises delivering the first negativepressure via the vacuum channel circumferentially around the valvecontrol region.
 4. The method of claim 1, further comprising closing thepump cassette membrane valve by applying positive pressure via thepressure delivery block to the inner side of the gasket valve controlregion against a raised wall of the valve seat surrounding an orifice ofthe pump cassette membrane valve.
 5. The method of claim 1, furthercomprising the valve control region applying pressure against the valveseat when the inner side of the gasket valve control region is exposedto atmospheric or ambient pressure.
 6. The method of claim 5, furthercomprising closing the membrane valve when the pump cassette is placedagainst the pressure delivery block.